Molecules having pesticidal utility, and intermediates, compositions, and processes, related thereto

ABSTRACT

This disclosure relates to the field of molecules having pesticidal utility against pests in Phyla Arthropoda, Mollusca, and Nematoda, processes to produce such molecules, intermediates used in such processes, compositions containing such molecules, and processes of using such molecules and compositions against such pests. These molecules and compositions may be used, for example, as acaricides, insecticides, miticides, molluscicides, and nematicides. This document discloses molecules having the following formula (“Formula One”).

CROSS REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of, and priority from, U.S.Provisional Patent Application Ser. Nos. 62/286,702 and 62/286,708 bothfiled Jan. 25, 2016, each of which are expressly incorporated byreference herein.

FIELD OF THIS DISCLOSURE

This disclosure relates to the field of molecules having pesticidalutility against pests in Phyla Arthropoda, Mollusca, and Nematoda,processes to produce such molecules, intermediates used in suchprocesses, pesticidal compositions containing such molecules, andprocesses of using such pesticidal compositions against such pests.These pesticidal compositions may be used, for example, as acaricides,insecticides, miticides, molluscicides, and nematicides.

BACKGROUND OF THIS DISCLOSURE

“Many of the most dangerous human diseases are transmitted by insectvectors” (Rivera et al.). “Historically, malaria, dengue, yellow fever,plague, filariasis, louse-borne typhus, trypanosomiasis, leishmaniasis,and other vector borne diseases were responsible for more human diseaseand death in the 17th through the early 20th centuries than all othercauses combined” (Gubler). Vector-borne diseases are responsible forabout 17% of the global parasitic and infectious diseases. Malaria alonecauses over 800,000 deaths a year, 85% of which occur in children underfive years of age. Each year there are about 50 to about 100 millioncases of dengue fever. A further 250,000 to 500,000 cases of denguehemorrhagic fever occur each year (Matthews). Vector control plays acritical role in the prevention and control of infectious diseases.However, insecticide resistance, including resistance to multipleinsecticides, has arisen in all insect species that are major vectors ofhuman diseases (Rivero et al.). Recently, more than 550 arthropod pestspecies have developed resistance to at least one pesticide (Whalon etal.).

Each year insects, plant pathogens, and weeds, destroy more than 40% ofall food production. This loss occurs despite the application ofpesticides and the use of a wide array of non-chemical controls, suchas, crop rotations, and biological controls. If just some of this foodcould be saved, it could be used to feed the more than three billionpeople in the world who are malnourished (Pimental).

Plant parasitic nematodes are among the most widespread pests, and arefrequently one of the most insidious and costly. It has been estimatedthat losses attributable to nematodes are from about 9% in developedcountries to about 15% in undeveloped countries. However, in the UnitedStates of America a survey of 35 States on various crops indicatednematode-derived losses of up to 25% (Nicol et al.).

It is noted that gastropods (slugs and snails) are pests of lesseconomic importance than other arthropods or nematodes, but in certainplaces they may reduce yields substantially, severely affecting thequality of harvested products, as well as, transmitting human, animal,and plant diseases. While only a few dozen species of gastropods areserious regional pests, a handful of species are important pests on aworldwide scale. In particular, gastropods affect a wide variety ofagricultural and horticultural crops, such as, arable, pastoral, andfiber crops; vegetables; bush and tree fruits; herbs; and ornamentals(Speiser).

Termites cause damage to all types of private and public structures, aswell as, to agricultural and forestry resources. In 2005, it wasestimated that termites cause over US$50 billion in damage worldwideeach year (Korb).

Consequently, for many reasons, including those mentioned above, thereis an on-going need for the costly (estimated to be about US$256 millionper pesticide in 2010), time-consuming (on average about 10 years perpesticide), and difficult, development of new pesticides (CropLifeAmerica).

DeMassey et al. discloses the following structure. For more detail,refer to US 2002/0068838.

CERTAIN REFERENCES CITED IN THIS DISCLOSURE

-   CropLife America, The Cost of New Agrochemical Product Discovery,    Development & Registration, and Research & Development predictions    for the Future, 2010.-   Gubler, D., Resurgent Vector-Borne Diseases as a Global Health    Problem, Emerging Infectious Diseases, Vol. 4, No. 3, p. 442-450,    1998.-   Korb, 1, Termites, Current Biology, Vol. 17, No. 23, 2007.-   Matthews, G., Integrated Vector Management: Controlling Vectors of    Malaria and Other Insect Vector Borne Diseases, Ch. 1, p. 1-2011.-   Nicol, J., Turner S.; Coyne, L.; den Nijs, L., Hocksland, L.,    Tahna-Maafi, Z., Current Nematode Threats to World Agriculture,    Genomic and Molecular Genetics of Plant—Nematode Interactions, p.    21-43, 2011).-   Pimental, D., Pest Control in World Agriculture, Agricultural    Sciences—Vol. II, 2009.-   Rivero, A., Vezilier, J., Weill, M., Read, A., Gandon, S., Insect    Control of Vector-Borne Diseases: When is Insect Resistance a    Problem? Public Library of Science Pathogens, Vol. 6, No. 8, p. 1-9,    2010.-   Speiser, B., Molluscicides, Encyclopedia of Pest Management, Ch.    219, p. 506-508, 2002.-   Whalon, M., Mota-Sanchez, D., Hollingworth, R., Analysis of Global    Pesticide Resistance in Arthropods, Global Pesticide Resistance in    Arthropods, Ch. 1, p. 5-33, 2008.

Definitions Used in this Disclosure

The examples given in these definitions are generally non-exhaustive andmust not be construed as limiting the disclosure. It is understood thata substituent should comply with chemical bonding rules and stericcompatibility constraints in relation to the particular molecule towhich it is attached. These definitions are only to be used for thepurposes of this disclosure.

“Active ingredient” means a material having activity useful incontrolling pests, and/or that is useful in helping other materials havebetter activity in controlling pests, examples of such materialsinclude, but are not limited to, acaricides, algicides, avicides,bactericides, fungicides, herbicides, insecticides, molluscicides,nematicides, rodenticides, virucides, antifeedants, bird repellents,chemosterilants, herbicide safeners, insect attractants, insectrepellents, mammal repellents, mating disrupters, plant activators,plant growth regulators, and synergists. Specific examples of suchmaterials include, but are not limited to, the materials listed inactive ingredient group alpha.

“Active ingredient group alpha” (hereafter “AIGA”) means collectivelythe following materials:

(1) (3-ethoxypropyl)mercury bromide, 1,2-dibromoethane,1,2-dichloroethane, 1,2-dichloropropane, 1,3-dichloropropene, 1-MCP,1-methylcyclopropene, 1-naphthol, 2-(octylthio)ethanol, 2,3,3-TPA,2,3,5-tri-iodobenzoic acid, 2,3,6-TBA, 2,4,5-T, 2,4,5-TB, 2,4,5-TP,2,4-D, 2,4-DB, 2,4-DEB, 2,4-DEP, 2,4-DES, 2,4-DP, 2,4-MCPA, 2,4-MCPB,2iP, 2-methoxyethylmercury chloride, 2-phenylphenol, 3,4-DA, 3,4-DB,3,4-DP, 3,6-dichloropicolinic acid, 4-aminopyridine, 4-CPA, 4-CPB,4-CPP, 4-hydroxyphenethyl alcohol, 8-hydroxyquinoline sulfate,8-phenylmercurioxyquinoline, abamectin, abamectin-aminomethyl, abscisicacid, ACC, acephate, acequinocyl, acetamiprid, acethion, acetochlor,acetofenate, acetophos, acetoprole, acibenzolar, acifluorfen, aclonifen,ACN, acrep, acrinathrin, acrolein, acrylonitrile, acypetacs,afidopyropen, afoxolaner, alachlor, alanap, alanycarb, albendazole,aldicarb, aldicarb sulfone, aldimorph, aldoxycarb, aldrin, allethrin,allicin, allidochlor, allosamidin, alloxydim, allyl alcohol, allyxycarb,alorac, alpha-cypermethrin, alpha-endosulfan, alphamethrin, altretamine,aluminium phosphide, aluminum phosphide, ametoctradin, ametridione,ametryn, ametryne, amibuzin, amicarbazone, amicarthiazol, amidithion,amidoflumet, amidosulfuron, aminocarb, aminocyclopyrachlor,aminopyralid, aminotriazole, amiprofos-methyl, amiprophos,amiprophos-methyl, amisulbrom, amiton, amitraz, amitrole, ammoniumsulfamate, amobam, amorphous silica gel, amorphous silicon dioxide,ampropylfos, AMS, anabasine, ancymidol, anilazine, anilofos, anisuron,anthraquinone, ante, apholate, aramite, arprocarb, arsenous oxide,asomate, aspirin, asulam, athidathion, atraton, atrazine, aureofungin,avermectin BI, AVG, aviglycine, azaconazole, azadirachtin, azafenidin,azamethiphos, azidithion, azimsulfuron, azinphosethyl, azinphos-ethyl,azinphosmethyl, azinphos-methyl, aziprotryn, aziprotryne, azithiram,azobenzene, azocyclotin, azothoate, azoxystrobin, bachmedesh, barban,barbanate, barium hexafluorosilicate, barium polysulfide, bariumsilicofluoride, barthrin, basic copper carbonate, basic copper chloride,basic copper sulfate, BCPC, beflubutamid, benalaxyl, benalaxyl-M,benazolin, bencarbazone, benclothiaz, bendaqingbingzhi, bendiocarb,bendioxide, benefin, benfluralin, benfuracarb, benfuresate,benmihuangcaoan, benodanil, benomyl, benoxacor, benoxafos, benquinox,bensulfuron, bensulide, bensultap, bentaluron, bentazon, bentazone,benthiavalicarb, benthiazole, benthiocarb, bentranil, benzadox,benzalkonium chloride, benzamacril, benzamizole, benzamorf, benzenehexachloride, benzfendizone, benzimine, benzipram, benzobicyclon,benzoepin, benzofenap, benzofluor, benzohydroxamic acid, benzomate,benzophosphate, benzothiadiazole, benzovindiflupyr, benzoximate,benzoylprop, benzthiazuron, benzuocaotong, benzyl benzoate,benzyladenine, berberine, beta-cyfluthrin, beta-cypermethrin,bethoxazin, BHC, bialaphos, bicyclopyrone, bifenazate, bifenox,bifenthrin, bifujunzhi, bilanafos, binapacryl, bingqingxiao,bioallethrin, bioethanomethrin, biopermethrin, bioresmethrin, biphenyl,bisazir, bismerthiazol, bismerthiazol-copper, bisphenylmercurymethylenedi(x-naphthalene-y-sulphonate), bispyribac, bistrifluron,bisultap, bitertanol, bithionol, bixafen, blasticidin-S, borax, Bordeauxmixture, boric acid, boscalid, BPPS, brassinolide, brassinolide-ethyl,brevicomin, brodifacoum, brofenprox, brofenvalerate, broflanilide,brofluthrinate, bromacil, bromadiolone, bromchlophos, bromethalin,bromethrin, bromfenvinfos, bromoacetamide, bromobonil, bromobutide,bromociclen, bromocyclen, bromo-DDT, bromofenoxim, bromofos,bromomethane, bromophos, bromophos-ethyl, bromopropylate, bromothalonil,bromoxynil, brompyrazon, bromuconazole, bronopol, BRP, BTH, bucarpolate,bufencarb, buminafos, bupirimate, buprofezin, Burgundy mixture,busulfan, busulphan, butacarb, butachlor, butafenacil, butam, butamifos,butane-fipronil, butathiofos, butenachlor, butene-fipronil, butethrin,buthidazole, buthiobate, buthiuron, butifos, butocarboxim, butonate,butopyronoxyl, butoxycarboxirn, butralin, butrizol, butroxydim, buturon,butylamine, butylate, butylchlorophos, butylene-fipronil, cacodylicacid, cadusafos, cafenstrole, calciferol, calcium arsenate, calciumchlorate, calcium cyanamide, calcium cyanide, calcium polysulfide,calvinphos, cambendichlor, camphechlor, camphor, captafol, captan,carbam, carbamorph, carbanolate, carbaril, carbaryl, carbasulam,carbathion, carbendazim, carbendazol, carbetamide, carbofenotion,carbofuran, carbon disulfide, carbon tetrachloride, carbonyl sulfide,carbophenothion, carbophos, carbosulfan, carboxazole, carboxide,carboxin, carfentrazone, carpropamid, cartap, carvacrol, carvone, CAVP,CDAA, CDEA, CDEC, cellocidin, CEPC, ceralure, cerenox, cevadilla,Cheshunt mixture, chinalphos, chinalphos-methyl, chinomethionat,chinomethionate, chiralaxyl, chitosan, chlobenthiazone, chlomethoxyfen,chloralose, chloramben, chloramine phosphorus, chloramphenicol,chloraniformethan, chloranil, chloranocryl, chlorantraniliprole,chlorazifop, chlorazine, chlorbenside, chlorbenzuron, chlorbicyclen,chlorbromuron, chlorbufam, chlordane, chlordecone, chlordimeform,chlorempenthrin, chloretazate, chlorethephon, chlorethoxyfos,chloreturon, chlorfenac, chlorfenapyr, chlorfenazole, chlorfenethol,chlorfenidim, chlorfenprop, chlorfenson, chlorfensulphide,chlorfenvinphos, chlorfenvinphos-methyl, chlorfluazuron, chlorflurazole,chlorflurecol, chlorfluren, chlorflurenol, chioridazon, chlorimuron,chlorinate, chlor-IPC, chlormephos, chlormequat, chlormesulone,chlormethoxynil, chlornidine, chlornitro en, chloroacetic acid,chlorobenzilate, chlorodinitronaphthalenes, chlorofenizon, chloroform,chloromebuform, chloromethiuron, chloroneb, chlorophacinone, chlorophos,chloropicrin, chloropon, chloropropylate, chlorothalonil, chlorotoluron,chloroxifenidim, chloroxuron, chloroxynil, chlorphonium, chiorphoxim,chlorprazophos, chlorprocarb, chlorpropham, chlorpyrifos,chlorpyrifos-methyl, chlorquinox, chlorsulfuron, chlorthal,chlorthiamid, chlorthiophos, chlortoluron, chiozolinate, chltosan,cholecalciferol, choline chloride, chromafenozide, cicloheximide,cimectacarb, cimetacarb, cinerin I, cinerin II, cinerins, cinidon-ethyl,cinmethylin, cinosulfuron, cintofen, ciobutide, cisanilide, cismethrin,clacyfos, clefoxydim, clenpirin, clenpyrin, clethodim, climbazole,cliodinate, clodinafop, cloethocarb, clofencet, clofenotane,clofentezine, clofenvinfos, clofibric acid, clofop, clomazone,clomeprop, clonitralid, cloprop, cloproxydim, clopyralid, cloquintocet,cloransulam, closantel, clothianidin, clotrimazole, cloxyfonac,cloxylacon, clozylacon, CMA, CMMP, CMP, CMU, codlelure, colecalciferol,colophonate, copper 8-quinolinolate, copper acetate, copperacetoarsenite, copper arsenate, copper carbonate basic, copperhydroxide, copper naphthenate, copper oleate, copper oxychloride, coppersilicate, copper sulfate, copper sulfate basic, copper zinc chromate,coumachlor, coumafene, coumafos, coumafuryl, coumaphos, coumatetralyl,coumethoxystrobin, coumithoate, coumoxystrobin, CPMC, CPMF, CPPC,credazine, cresol, cresylic acid, crimidine, crotamiton, crotoxyfos,crotoxyphos, crufomate, cryolite, cue-lure, cufraneb, cumyleron,cumyluron, cuprobam, cuprous oxide, curcumenol, CVMP, cyanamide,cyanatryn, cyanazine, cyanofenphos, cyanogen, cyanophos, cyanthoate,cyantraniliprole, cyanuric acid, cyazofamid, cybutryne, cyclafuramid,cyclanilide, cyclaniliprole, cyclethrin, cycloate, cycloheximide,cycloprate, cycloprothrin, cyclopyrimorate, cyclosulfamuron, cycloxydim,cycluron, cyenopyrafen, cyflufenamid, cyflumetofen, cyfluthrin,cyhalofop, cyhalothrin, cyhexatin, cymiazole, cymoxanil, cyometrinil,cypendazole, cypermethrin, cyperquat, cyphenothrin, cyprazine,cyprazole, cyproconazole, cyprodinil, cyprofuram, cypromid,cyprosulfamide, cyromazine, cythioate, cytrex, daimuron, dalapon,daminozide, dayoutong, dazomet, DBCP, d-camphor, DCB, DCIP, DCPA, DCPTA,DCU, DDD, DDPP, DDT, DDVP, debacarb, decafentin, decamethrin,decarbofuran, deet, dehydroacetic acid, deiquat, delachior, delnav,deltamethrin, demephion, demephion-O, demephion-S, derneton,demeton-methyl, demeton-O, demeton-O-methyl, demeton-S,demeton-S-methyl, demeton-S-methyl sulphone, demeton-S-methylsulphon,DEP, depallethrine, derris, desmedipham, desmetryn, desmetryne,d-fanshiluquebingjuzhi, diafenthiuron, dialifor, dialifos, diallate,diamidafos, dianat, diatomaceous earth, diatomite, diazinon, dibrom,dibutyl phthalate, dibutyl succinate, dicamba, dicapthon, dichlobenil,dichlofenthion, dichiofluanid, dichlone, dichloralurea, dichlorbenzuron,dichlorfenidim, dichlorflurecol, dichlorflurenol, dichiormate,dichiormid, dichloromethane, dicloromezotiaz, dichlorophen, dichlorprop,dichlorprop-P, dichlorvos, dichlozolin, dichlozoline, diclobutrazol,diclocymet, diclofop, diclomezine, dicloran, diclosulam, dicofol,dicophane, dicournarol, dicresyl, dicrotophos, dicryl, dicumarol,dicyclanil, dicyclonon, dieldrin, dienochlor, diethamquat, diethatyl,diethion, diethion, diethofencarb, dietholate, diethon, diethylpyrocarbonate, diethyltoluamide, difenacoum, difenoconazole,difenopenten, difenoxuron, difenzoquat, difethialone, diflovidazin,diflubenzuron, diflufenican, diflufenicanil, diflufenzopyr,diflumetorim, dikegulac, dilor, dimatif, dimefluthrin, dimefox,dimefuron, dimehypo, dirnepiperate, dimetachlone, dimetan, dimethacarb,dimethachlone, dimethachior, dimethametryn, dimethenamid,dimethenamid-P, dimethipin, dimethirimol, dimethoate, dimethomorph,dimethrin, dimethyl carbate, dimethyl disulfide, dimethyl phthalate,dimethylvinphos, dimetilan, dimexano, dimidazon, dimoxystrobin,dimpylate, dimuron, dinex, dingjunezuo, diniconazole, diniconazole-M,dinitramine, dinitrophenols, dinobuton, dinocap, dinocap-4, dinocap-6,dinocton, dinofenate, dinopenton, dinoprop, dinosam, dinoseb,dinosulfon, dinotefuran, dinoterb, dinoterbon, diofenolan,dioxabenzofos, dioxacarb, dioxathion, dioxation, diphacin, diphacinone,diphenadione, diphenarnid, diphenamide, diphenyl sulfone, diphenylamine,diphenylsulphide, diprogulic acid, dipropalin, dipropetryn, dipterex,dipymetitrone, dipyrithione, diquat, disodium tetraborate, disosultap,disparlure, disugran, disul, disulfiram, disulfoton, ditalimfos,dithianon, dithicrofos, dithioether, dithiométon, dithiopyr, diuron,dixanthogen, d-limonene, DMDS, DMPA, DNOC, dodemorph, dodicin, dodine,dofenapyn, doguadine, dominicalure, doramectin, DPC, drazoxolon, DSMA,d-trans-allethrin, d-trans-resmethrin, dufulin, dymron, EBEP, EBP,ebufos, ecdysterone, echlomezol, EDB, EDC, EDDP, edifenphos, eglinazine,emamectin, EMPC, empenthrin, enadenine, endosulfan, endothal, endothall,endothion, endrin, enestroburin, enilconazole, enoxastrobin,ephirsulfonate, EPN, epocholeone, epofenonane, epoxiconazole,eprinomectin, epronaz, EPTC, erbon, ergocalciferol, erlujixiancaoan,esdépalléthrine, esfenvalerate, ESP, esprocarb, etacelasil, etaconazole,etaphos, etem, ethaboxam, ethachlor, ethalfluralin, ethametsulfuron,ethaprochlor, ethephon, ethidimuron, ethiofencarb, ethiolate, ethion,ethiozin, ethiprole, ethirimol, ethoate-methyl, ethobenzanid,ethofumesate, ethohexadiol, ethoprop, ethoprophos, ethoxyfen,ethoxyquin, ethoxysulfuron, ethychlozate, ethyl formate, ethylpyrophosphate, ethylan, ethyl-DDD, ethylene, ethylene dibromide,ethylene dichloride, ethylene oxide, ethylicin, ethylmercury2,3-dihydroxypropyl mercaptide, ethylmercury acetate, ethylmercurybromide, ethylmercury chloride, ethylmercury phosphate, etinofen, ETM,etnipromid, etobenzanid, etofenprox, etoxazole, etridiazole, etrimfos,étrimphos, eugenol, EXD, famoxadone, famphur, fenac, fenamidone,fenaminosulf, fenaminstrobin, fenamiphos, fenapanil, fenarimol,fenasulam, fenazaflor, fenazaquin, fenbuconazole, fenbutatin oxide,fenchlorazole, fenchlorphos, fenclofos, fenclorim, fenethacarb,fenfluthrin, fenfuram, fenhexamid, fenidin, fenitropan, fenitrothion,fenizon, fenjuntong, fenobucarb, fenolovo, fenoprop, fenothiocarb,fenoxacrim, fenoxanil, fenoxaprop, fenoxaprop-P, fenoxasulfone,fenoxycarb, fenpiclonil, fenpirithrin, fenpropathrin, fenpropidin,fenpropimorph, fenpyrazamine, fenpyroximate, fenquinotrione, fenridazon,fenson, fensulfothion, fenteracol, fenthiaprop, fenthion,fenthion-ethyl, fentiaprop, fentin, fentrazamide, fentrifanil, fenuron,fenuron-TCA, fenvalerate, ferbam, ferimzone, ferric phosphate, ferroussulfate, fipronil, flamprop, flamprop-M, flazasulfuron, flocoumafen,flometoquin, flonicamid, florasularn, fluacrypyrim, fluazifop,fluazifop-P, fluazinam, fluazolate, fluazuron, flubendiamide,flubenzimine, flubrocythrinate, flucarbazone, flucetosulfuron,fluchloralin, flucofuron, flucycloxuron, flucythrinate, fludioxonil,fluénéthyl, fluenetil, fluensulfone, flufenacet, flufenerim, flufenican,flufenoxuron, flufenoxystrobin, flufenprox, flufenpyr, flufenzine,flufiprole, fluhexafon, flumethrin, flumetover, flumetralin,flumetsulam, flumezin, flumiclorac, flumioxazin, flumipropyn, flumorph,fluometuron, fluopicolide, fluopyram, fluorbenside, fluoridamid,fluoroacetamide, fluoroacetic acid, fluorochloridone, fluorodifen,fluoroglycofen, fluoroimide, fluoromide, fluoromidine, fluoronitrofen,fluoroxypyr, fluothiuron, fluotrimazole, fluoxastrobin, flupoxam,flupropacil, flupropadine, flupropanate, flupyradifurone,flupyrsulfuron, fluquinconazole, fluralaner, flurazole, flurecol,flurenol, fluridone, flurochloridone, fluromidine, fluroxypyr,flurprimidol, flursulamid, flurtamone, flusilazole, flusulfamide,flutenzine, fluthiacet, fluthiamide, flutianil, flutolanil, flutriafol,fluvalinate, fluxapyroxad, fluxofenim, folpel, folpet, fomesafen,fonofos, foramsulfuron, forchlorfenuron, formaldehyde, formetanate,formothion, formparanate, fosamine, fosetyl, fosmethilan, fospirate,fosthiazate, fosthietan, frontalis, fthalide, fuberidazole, fucaojing,fucaomi, fujunmanzhi, fulumi, fumarin, funaihecaoling, fuphenthiourea,furalane, furalaxyl, furamethrin, furametpyr, furan tebufenozide,furathiocarb, furcarbanil, furconazole, furconazole-cis, furethrin,furfural, furilazole, furmecyclox, furophanate, furyloxyfen, gamma-BHC,gamma-cyhalothrin, gamma-HCH, genit, gibberellic acid, gibberellin A3,gibberellins, gliftor, glitor, glucochloralose, glufosinate,glufosinate-P, glyodin, glyoxime, glyphosate, glyphosine, gossyplure,grandlure, griseofulvin, guanoctine, guazatine, halacrinate, halauxifen,halfenprox, halofenozide, halosafen, halosulfuron, haloxydine,haloxyfop, haloxyfop-P, haloxyfop-R, HCA, HCB, HCH, hemel, hempa, HEAD,heptachlor, heptafluthrin, heptenophos, heptopargil, herbimycin,herbimycin A, heterophos, hexachlor, hexachloran, hexachloroacetone,hexachlorobenzene, hexachlorobutadiene, hexachlorophene, hexaconazole,hexaflumuron, hexafluoramin, hexaflurate, hexalure, hexamide,hexazinone, hexyithiofos, hexythiazox, HHDN, holosulf, homobrassinolide,huancaiwo, huanchongjing, huangcaoling, huanjunzuo, hydramethylnon,hydrargaphen, hydrated lime, hydrogen cyanamide, hydrogen cyanide,hydroprene, hydroxyisoxazole, hymexazol, hyquincarb, IAA, IBA, IBP,icaridin, imazalil, imazamethabenz, imazamox, imazapic, imazapyr,imazaquin, imazethapyr, imazosulfuron, imibenconazole, imicyafos,imidacloprid, imidaclothiz, iminoctadine, imiprothrin, inabenfide,indanofan, indaziflam, indoxacarb, inezin, infusorial earth, iodobonil,iodocarb, iodofenphos, iodomethane, iodosulfuron, iofensulfuron,ioxynil, ipazine, IPC, ipconazole, ipfencarbazone, ipfentrifluconazole,iprobenfos, iprodione, iprovalicarb, iprymidam, ipsdienol, ipsenol,IPSP, IPX, isamidofos, isazofos, isobenzan, isocarbamid, isocarbamide,isocarbophos, isocil, isodrin, isofenphos, isofenphos-methyl,isofetamid, isolan, isomethiozin, isonoruron, isopamphos, isopolinate,isoprocarb, isoprocil, isopropalin, isopropazol, isoprothiolane,isoproturon, isopyrazam, isopyrimol, isothioate, isotianil, isouron,isovaledione, isoxaben, isoxachlortole, isoxadifen, isoxaflutole,isoxapyrifop, isoxathion, isuron, ivermectin, ixoxaben, izopamfos,izopamphos, japonilure, japothrins, jasmolin I, jasmolin II, jasmonicacid, jiahuangchongzong, jiajizengxiaolin, jiaxiangjunzhi, jiecaowan,jiecaoxi, Jinganmycin A, jodfenphos, juvenile hormone I, juvenilehormone II, juvenile hormone III, kadethrin, kappa-bifenthrin,kappa-tefluthrin, karbutilate, karetazan, kasugamycin, kejunlin,kelevan, ketospiradox, kieselguhr, kinetin, kinoprene, kira axyl,kresoxim-methyl, kuicaoxi, lactofen, iarnbda-cyhalothrin, latilure, leadarsenate, lenacil, lepimectin, leptophos, lianbenjingzhi, lime sulfur,lindane, lineatin, linuron, lirimfos, litlure, looplure, lufenuron,ICixiancaolin, lvdingjunzhi, Ivfumijvzhi, lvxiancaolin, lythidathion,M-74, M-81, MAA, magnesium phosphide, malathion, maldison, maleichydrazide, malonoben, maltodextrin, MAMA, mancopper, mancozeb,mandestrobin, mandipropamid, maneb, matrine, mazidox, MCC, MCP, MCPA,MCPA-thioethyl, MCPB, MCPP, mebenil, mecarbam, mecarbinzid, mecarphon,mecoprop, mecoprop-P, medimeform, medinoterb, medlure, mefenacet,mefenoxam, mefenpyr, mefluidide, megatomoic acid, melissyl alcohol,melitoxin, MEMC, menazon, MEP, mepanipyrim, meperfluthrin, mephenate,mephosfolan, mepiquat, mepronil, meptyldinocap, mercaptodimethur,mercaptophos, mercaptophos thiol, mercaptothion, mercuric chloride,mercuric oxide, mercurous chloride, merphos, merphos oxide, mesoprazine,mesosulfuron, mesotrione, mesulfen, mesulfenfos, mesulphen, metacresol,metaflumizone, metalaxyl, metalaxyl-M, metaldehyde, metam, metamifop,metamitron, metaphos, metaxon, metazachlor, metazosulfuron, metazoxolon,metconazole, metepa, metflurazon, methabenzthiazuron, methacrifos,methalpropalin, metham, methamidophos, methasulfocarb, methazole,methfuroxam, methibenzuron, methidathion, methiobencarb, methiocarb,methiopyrisulfuron, methiotepa, methiozolin, methiuron, methocrotophos,metholcarb, methometon, methomyl, methoprene, methoprotryn,methoprotryne, methoquin-butyl, methothrin, methoxychlor,methoxyfenozide, methoxyphenone, methyl apholate, methyl bromide, methyleugenol, methyl iodide, methyl isothiocyanate, methyl parathion,methylacetophos, methylchloroform, methyldithiocarbamic acid,methyldymron, methylene chloride, methyl-isofenphos, methylmercaptophos,methylmercaptophos oxide, methylmercaptophos thiol, methylmercurybenzoate, methylmercury dicyandiamide, methylmercurypentachlorophenoxide, methylneodecanamide, methylnitrophos,methyltriazothion, metiozolin, metiram, metiram-zinc, metobenzuron,metobromuron, metofluthrin, metolachlor, metolcarb, metometuron,metominostrobin, metosulam, metoxadiazone, metoxuron, metrafenone,metriam, metribuzin, metrifonate, metriphonate, metsulfovax,metsulfuron, mevinphos, mexacarbate, miechuwei, mieshuan, miewenjuzhi,milbemectin, milbemycin oxime, milneb, mima2nan, mipafox, MIPC, mirex,MNAF, moguchun, molinate, molosultap, momfluorothrin, monalide,monisuron, monoamitraz, monochloroacetic add, monocrotophos,monolinuron, monomehypo, monosulfiram, monosulfuron, monosultap,monuron, monuron-TCA, morfamquat, moroxydine, morphothion, morzid,moxidectin, MPMC, MSMA, MTMC, muscalure, myclobutanil, myclozolin,myricyl alcohol, N-(ethylmercury)-p-toluenesulphonanilide, NAA, NAAm,nabam, naftalofos, naled, naphthalene, naphthaleneacetamide, naphthalicanhydride, naphthalophos, naphthoxyacetic acids, naphthylacetic acids,naphthylindane-1,3-diones, naphthyloxyacetic acids, naproanilide,napropamide, napropamide-M, naptalam, natamycin, NBPOS, neburea,neburon, nendrin, neonicotine, nichlorfos, niclofen, niclosamide,nicobifen, nicosulfuron, nicotine, nicotine sulfate, nifluridide,nikkomycins, NIP, nipyraclofen, nipyralofen, nitenpyram, nithiazine,nitralin, nitrapyrin, nitrilacarb, nitrofen, nitrofluorfen,nitrostyrene, nitrothal-isopropyl, nobormide, nonanol, norbormide,norea, norfiurazon, nornicotine, noruron, novaluron, noviflumuron, NPA,nuarimol, nuranone, OCH, octachlorodipropyl ether, octhilinone,o-dichlorobenzene, ofurace, omethoate, o-phenylphenol, orbencarb,orfralure, orthobencarb, ortho-dichlorobenzene, orthosulfamuron,oryctalure, orysastrobin, oryzalin, osthol, osthole, ostramone, ovatron,ovex, oxabetrinil, oxadiargyl, oxadiazon, oxadixyl, oxamate, oxamyl,oxapyrazon, oxapyrazone, oxasulfuron, oxathiapiprolin, oxaziclomefone,oxine-copper, oxine-Cu, oxolinic acid, oxpoconazole, oxycarboxin,oxydemeton-methyl, oxydeprofos, oxydisulfoton, oxyenadenine,oxyfluorfen, oxymatrine, oxytetracycline, oxythioquinox, PAC,paclobutrazol, paichongding, palléthrine, PAP, para-dichlorobenzene,parafluron, paraquat, parathion, parathion-methyl, parinol, Paris green,PCNB, PCP, PCP-Na, p-dichlorobenzene, PDJ, pebulate, pedinex,pefurazoate, pelargonic add, penconazole, pencycuron, pendimethalin,penfenate, penflufen, penfluron, penoxalin, penoxsulam,pentachlorophenol, pentachlorophenyl laurate, pentanochlor,penthiopyrad, pentmethrin, pentoxazone, perchlordecone, perfluidone,permethrin, pethoxamid, PHC, phenamacril, phenamacril-ethyl,phénaminosulf, phenazine oxide, phénétacarbe, phenisopham, phenkapton,phenmedipham, phenmedipham-ethyl, phenobenzuron, phenothiol, phenothrin,phenproxide, phenthoate, phenylmercuriurea, phenylmercury acetate,phenylmercury chloride, phenylmercury derivative of pyrocatechol,phenylmercury nitrate, phenylmercury salicylate, phorate, phosacetim,phosalone, phosametine, phosazetim, phosazetin, phoscyclotin,phosdiphen, phosethyl, phosfolan, phosfolan-methyl, phosglycin, phosmet,phosnichior, phosphamide, phosphamidon, phosphine, phosphinothricin,phosphocarb, phosphorus, phostin, phoxim, phoxim-methyl, phthalide,phthalophos, phthalthrin, picarbutrazox, picaridin, piclorarn,picolinafen, picoxystrobin, pimaricin, pindone, pinoxaden, piperalin,piperazine, piperonyl butoxide, piperonyl cyclonene, piperophos,piproctanly, piproctanyl, piprotal, pirimetaphos, pirimicarb, piriminil,pirimioxyphos, pirimiphos-ethyl, pirimiphos-methyl, pival, pivaldione,plifenate, PMA, PMP, polybutenes, polycarbamate, polychlorcamphene,polyethoxyquinoline, polyoxin D, polyoxins, polyoxorim, polythialan,potassium arsenite, potassium azide, potassium cyanate, potassiumethylxanthate, potassium naphthenate, potassium polysulfide, potassiumthiocyanate, pp′-DDT, prallethrin, precocene precocene II, precoceneIII, pretilachlor, primidophos, primisulfuron, probenazole, prochloraz,proclonol, procyazine, procymidone, prodiamine, profenofos, profluazol,profluralin, profluthrin, profoxydim, profurite-aminium, proglinazine,prohexadione, prohydrojasmon, promacyl, promecarb, prometon, prometryn,prometryne, promurit, pronamide, propachlor, propafos, propamidine,propamocarb, propanil, propaphos, propaquizafop, propargite,proparthrin, propazine, propetamphos, propham, propiconazole, propidine,propineb, propisochior, propoxur, propoxycarbazone, propyl isome,propyrisulfuron, propyzamide, proquinazid, prosuler, prosulfalin,prosulfocarb, prosulfuron, prothidathion, prothiocarb, prothioconazole,prothiofos, prothoate, protrifenbute, proxan, prymidophos, prynachior,psoralen, psoralene, pydanon, pyflubumide, pymetrozine, pyracarbolid,pyraclofos, pyraclonil, pyraclostrobin, pyraflufen, pyrafluprole,pyramat, pyrametostrobin, pyraoxystrobin, pyrasulfotole, pyraziflurnid,pyrazolate, pyrazolynate, pyrazon, pyrazophos, pyrazosulfuron,pyrazothion, pyrazoxyfen, pyresmethrin, pyrethrin I, pyrethrin II,pyrethrins, pyribambenz-isopropyl, pyribambenz-propyl, pyribencarb,pyribenzoxim, pyributicarb, pyriclor, pyridaben, pyridafol, pyridalyl,pyridaphenthion, pyridaphenthione, pyridate, pyridinitril, pyrifenox,pyrifluquinazon, pyriftalid, pyrimétaphos, pyrimethanil, pyrimicarbe,pyrimidifen, pyrirninobac, pyriminostrobin, pyrimiphos-éthyl,pyrimiphos-méthyl, pyrimisulfan, pyrimitate, pyrinuron, pyriofenone,pyriprole, pyripropanol, pyriproxyfen, pyrisoxazole, pyrithiobac,pyrolan, pyroquilon, pyroxasulfone, pyroxsulam, pyroxychior, pyroxyfur,qincaosuan, qingkuling, quassia, quinacetol, quinalphos,quinalphos-methyl, quinazamid, quinclorac, quinconazole, quinmerac,quinoclamine, quinomethionate, quinonamid, quinothion, quinoxyfen,quintiofos, quintozene, quizalofop, quizalofop-P, quwenzhi, quyingding,rabenzazole, rafoxanide, R-diniconazole, rebemide, reglone, renriduron,rescalure, resmethrin, rhodethanil, rhodojaponin-III, ribavirin,rimsulfuron, rizazole, R-metalaxyl, rodethanil, runnel, rotenone,ryania, sabadilla, saflufenacil, saijunmao, saisentong, salicylanilide,salifluofen, sanguinarine, santonin, S-bioallethrin, schradan,scilliroside, sebuthylazine, secbumeton, sedaxane, selamectin,semiamitraz, sesamex, sesamolin, sesone, sethoxydim, sevin,shuangjiaancaolin, shuangjianancaolin, S-hydroprene, siduron,sifumijvzhi, siglure, silafluofen, silatrane, silica aerogel, silicagel, silthiofam, silthiopham, silthiophan, silvex, simazine,simeconazole, simeton, simetryn, simetryne, sintofen, S-kinoprene,slaked lime, SMA, S-methoprene, S-metolachlor, sodium arsenite, sodiumazide, sodium chlorate, sodium cyanide, sodium fluoride, sodiumfluoroacetate, sodium hexafluorosilicate, sodium naphthenate, sodiumo-phenylphenoxide, sodium orthophenylphenoxide, sodiumpentachlorophenate, sodium pentachlorophenoxide, sodium polysulfide,sodium silicofluoride, sodium tetrathiocarbonate, sodium thiocyanate,solan, sophamide, spinetoram, spinosad, spirodiclofen, spiromesifen,spirotetramat, spiroxamine, stirofos, streptomycin, strychnine,sulcatol, sulcofuron, sulcotrione, sulfallate, sulfentrazone, sulfiram,sulfluramid, sulfodiazole, sulfometuron, sulfosate, sulfosulfuron,sulfotep, sulfotepp, sulfoxaflor, sulfoxide, sulfoxime, sulfur, sulfuricacid, sulfuryl fluoride, sulglycapin, sulphosate, sulprofos, sultropen,swep, tau-fluvalinate, tavron, tazirncarb, TBTO, TBZ, TCA, TCBA, TCMTB,TCNB, TDE, tebuconazole, tebufenozide, tebufenpyrad, tebufloquin,tebupirimfos, tebutam, tebuthiuron, tecloftalam, tecnazene, tecoram,tedion, teflubenzuron, tefluthrin, tefuryltrione, tembotrione, temefos,temephos, tepa, TEPP, tepraloxydim, teproloxydim, terallethrin,terbacil, terbucarb, terbuchlor, terbufos, terbumeton, terbuthylazine,terbutol, terbutryn, terbutryne, terraclor, terramicin, terramycin,tetcyclacis, tetrachloroethane, tetrachlorvinphos, tetraconazole,tetradifon, tetradisul, tetrafluron, tetramethrin, tetramethylfluthrin,tetramine, tetranactin, tetraniliprole, tetrapion, tetrasul, thalliumsulfate, thallous sulfate, thenylchlor, theta-cypermethrin,thiabendazole, thiacloprid, thiadiazine, thiadifluor, thiamethoxam,thiameturon, thiapronil, thiazafluron, thiazfluron, thiazone, thiazopyr,thicrofos, thicyofen, thidiazimin, thidiazuron, thiencarbazone,thifensulfuron, thifluzamide, thimerosal, thimet, thiobencarb,thiocarboxime, thiochlorfenphim, thiochlorphenphime,thiocyanatodinitrobenzenes, thiocyclam, thiodan, thiodiazole-copper,thiodicarb, thiofanocarb, thiofanox, thiofluoximate, thiohempa,thiomersal, thiometon, thionazin, thiophanate, thiophanate-ethyl,thiophanate-methyl, thiophos, thioquinox, thiosemicarbazide, thiosultap,thiotepa, thioxamyl, thiram, thiuram, thuringiensis, tiabendazole,tiadinil, tiafenacil, tiaojiean, TIBA, tifatol, tiocarbazil, tioclorim,tioxazafen, tioxymid, tirpate, TMTD, tolclofos-methyl, tolfenpyrad,tolprocarb, tolpyralate, tolyfluanid, tolylfluanid, tolylmercuryacetate, tornarin, topramezone, toxaphene, TPN, tralkoxydim,tralocythrin, tralomethrin, tralopyril, transfluthrin, transpermethrin,tretamine, triacontanol, triadimefon, triadimenol, triafamone,triallate, tri-allate, triamiphos, triapenthenol, triarathene,triarimol, triasulfuron, triazamate, triazbutil, triaziflam, triazophos,triazothion, triazoxide, tribasic copper chloride, tribasic coppersulfate, tribenuron, tribufos, tributyltin oxide, tricamba, trichlamide,trichlopyr, trichlorfon, trichlorrnetaphos-3, trichloronat,trichloronate, trichlorotrinitrobenzenes, trichlorphon, triclopyr,triclopyricarb, tricresol, tricyclazole, tricyclohexyltin hydroxide,tridemorph, tridiphane, trietazine, trifenmorph, trifenofos,trifloxystrobin, trifloxysulfuron, trifludimoxazin, triflumezopyrim,triflumizole, triflumuron, trifluralin, triflusulfuron, trifop,trifopsime, triforine, trihydroxytriazine, trimedlure, trimethacarb,trimeturon, trinexapac, triphenyltin, triprene, tripropindan,triptolide, tritac, trithialan, triticonazole, tritosulfuron,trunc-call, tuoyelin, uniconazole, uniconazole-P, urbacide, uredepa,valerate, validamycin, validamycin A, valifenalate, valone, vamidothion,vangard, vaniliprole, vernolate, vinclozolin, vitamin D3, warfarin,xiaochongliulin, xinjunan, xiwojunan, xiwojunzhi, XMC, xylachlor,xylenols, xylylcarb, xymiazole, yishijing, zarilamid, zeatin,zengxiaoan, zengxiaolin, zeta-cypermethrin, zinc naphthenate, zincphosphide, zinc thiazole, zinc thiozole, zinc trichlorophenate, zinctrichlorophenoxide, zineb, ziram, zolaprofos, zoocoumarin, zoxamide,zuoanjunzhi, zuocaoan, zuojunzhi, zuomihuanglong, α-chlorohydrin,α-ecdysone, α-MUitiStriatin, α-naphthaleneacetic acids, and β-ecdysone;

(2) the following molecule

N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-N-ethyl-3-((3,3,3-trifluoropropyl)thio)propanamide

In this document, this molecule, for ease of use, is named as “AI-1;”

(3) a molecule known as Lotilaner which has the following structure

and

(4) the following molecules in Table A

TABLE A Structure of M-active ingredients Name Structure M1

R = CH, N R₁ = H, Me M2

X = F, Cl R = H, F M3

M4

M5

M6

As used in this disclosure, each of the above is an active ingredient,and two or more are active ingredients. For more information consult the“COMPENDIUM OF PESTICIDE COMMON NAMES” located at Alanwood.net andvarious editions, including the on-line edition, of “THE PESTICIDEMANUAL” located at bcpcdata.com.

The term “alkenyl” means an acyclic, unsaturated (at least onecarbon-carbon double bond), branched or unbranched, substituentconsisting of carbon and hydrogen, for example, vinyl, allyl, butenyl,pentenyl, and hexenyl.

The term “alkenyloxy” means an alkenyl further consisting of acarbon-oxygen single bond, for example, allyloxy, butenyloxy,pentenyloxy, hexenyloxy.

The term “alkoxy” means an alkyl further consisting of a carbon-oxygensingle bond, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy,isobutoxy, and tert-butoxy.

The term “alkyl” means an acyclic, saturated, branched or unbranched,substituent consisting of carbon and hydrogen, for example, methyl,ethyl, propyl, isopropyl, butyl, and tert-butyl.

The term “alkynyl” means an acyclic, unsaturated (at least onecarbon-carbon triple bond), branched or unbranched, substituentconsisting of carbon and hydrogen, for example, ethynyl, propargyl,butynyl, and pentynyl.

The term “alkynyloxy” means an alkynyl further consisting of acarbon-oxygen single bond, for example, pentynyloxy, hexynyloxy,heptynyloxy, and octynyloxy.

The term “aryl” means a cyclic, aromatic substituent consisting ofhydrogen and carbon, for example, phenyl, naphthyl, and biphenyl.

The term “biopesticide” means a microbial biological pest control agentwhich, in general, is applied in a similar manner to chemicalpesticides. Commonly they are bacterial, but there are also examples offungal control agents, including Trichoderma spp. and Ampelomycesquisqualis. One well-known biopesticide example is Bacillusthuringiensis, a bacterial disease of Lepidoptera, Coleoptera, andDiptera. Biopesticides include products based on:

(1) entomopathogenic fungi (e.g. Metarhizium anisopliae);

(2) entomopathogenic nematodes (e.g. Steinernema feltiae); and

(3) entomopathogenic viruses (e.g. Cydia pomonella granulovirus).

Other examples of entomopathogenic organisms include, but are notlimited to, baculoviruses, protozoa, and Microsporidia. For theavoidance of doubt biopesticides are considered to be activeingredients.

The term “cycloalkenyl” means a monocyclic or polycyclic, unsaturated(at least one carbon-carbon double bond) substituent consisting ofcarbon and hydrogen, for example, cyclobutenyl, cyclopentenyl,cyclohexenyl, norbornenyl, bicyclo[2.2.2]octenyl, tetrahydronaphthyl,hexahydronaphthyl, and octahydronaphthyl.

The term “cycloalkenyloxy” means a cycloalkenyl further consisting of acarbon-oxygen single bond, for example, cyclobutenyloxy,cyclopentenyloxy, norbornenyloxy, and bicyclo[2.2.2]octenyloxy.

The term “cycloalkyl” means a monocyclic or polycyclic, saturatedsubstituent consisting of carbon and hydrogen, for example, cyclopropyl,cyclobutyl, cyclopentyl, norbornyl, bicyclo[2.2.2]octyl, anddecahydronaphthyl.

The term “cycloalkoxy” means a cycloalkyl further consisting of acarbon-oxygen single bond, for example, cyclopropyloxy, cyclobutyloxy,cyclopentyloxy, norbornyloxy, and bicyclo[2.2.2]octyloxy.

The term “halo” means fluoro, chloro, bromo, and iodo.

The term “haloalkoxy” means an alkoxy further consisting of, from one tothe maximum possible number of identical or different, halos, forexample, fluoromethoxy, trifluoromethoxy, 2,2-difluoropropoxy,chloromethoxy, trichloromethoxy, 1,1,2,2-tetrafluoroethoxy, andpentafluoroethoxy.

The term “haloalkyl” means an alkyl further consisting of, from one tothe maximum possible number of, identical or different, halos, forexample, fluoromethyl, trifluoromethyl, 2,2-difluoropropyl,chloromethyl, trichloromethyl, and 1,1,2,2-tetrafluoroethyl.

The term “heterocyclyl” means a cyclic substituent that may be aromatic,fully saturated, or partially or fully unsaturated, where the cyclicstructure contains at least one carbon and at least one heteroatom,where said heteroatom is nitrogen, sulfur, or oxygen. Examples are:

(1) aromatic heterocyclyl substituents include, but are not limited to,benzofuranyl, benzoisothiazolyl, benzoisoxazolyl, benzoxazolyl,benzothienyl, benzothiazolyl cinnolinyl, furanyl, indazolyl, indolyl,imidazolyl, isoindolyl, isoquinolinyl, isothiazolyl, isoxazolyl,oxadiazoyl, oxazolinyl, oxazolyl, phthalazinyl, pyrazinyl, pyrazolinyl,pyrazolyl, pyridazinyl, pyridyl, pyrimidinyl, pyrrolyl, quinazolinyl,quinolinyl, quinoxalinyl, tetrazolyl, thiazolinyl, thiazolyl, thienyl,triazinyl, and triazolyl;

(2) fully saturated heterocyclyl substituents include, but are notlimited to, piperazinyl, piperidinyl, morpholinyl, pyrrolidinyl,tetrahydrofuranyl, and tetrahydropyranyl;

(3) partially or fully unsaturated heterocyclyl substituents include,but are not limited to, 1,2,3,4-tetrahydro-quinolinyl,4,5-dihydro-oxazolyl, 4,5-dihydro-1H-pyrazolyl, 4,5-dihydro-isoxazolyl,and 2,3-dihydro-[1,3,4]-oxadiazolyl; and

(4) Additional examples of heterocyclyls include the following:

The term “locus” means a habitat, breeding ground, plant, seed, soil,material, or environment, in which a pest is growing, may grow, or maytraverse, for example, a locus may be: where crops, trees, fruits,cereals, fodder species, vines, turf, and/or ornamental plants aregrowing; where domesticated animals are residing; the interior orexterior surfaces of buildings (such as places where grains are stored);the materials of construction used in buildings (such as impregnatedwood); and the soil around buildings.

The phrase “MoA Material” means a material having a mode of action(“MoA”) as indicated in IRAC MoA Classification v. 7.3, located atirac-online.org., which describes:

(1) Acetylcholinesterase (ACNE) inhibitors;

(2) GABA-gated chloride channel antagonists;

(3) Sodium channel modulators;

(4) Nicotinic acetylcholine receptor (nAChR) agonists;

(5) Nicotinic acetylcholine receptor (nAChR) allosteric activators;

(6) Chloride channel activators;

(7) Juvenile hormone mimics;

(8) Miscellaneous nonspecific (multi-site) inhibitors;

(9) Modulators of Chordotonal Organs;

(10) Mite growth inhibitors;

(11) Microbial disruptors of insect midgut membranes;

(12) Inhibitors of mitochondrial ATP synthase;

(13) Uncouplers of oxidative phosphorylation via disruption of theproton gradient;

(14) Nicotinic acetylcholine receptor (nAChR) channel blockers;

(15) Inhibitors of chitin biosynthesis, type 0;

(16) Inhibitors of chitin biosynthesis, type 1;

(17) Moulting disruptor, Dipteran;

(18) Ecdysone receptor agonists;

(19) Octopamine receptor agonists;

(20) Mitochondrial complex III electron transport inhibitors;

(21) Mitochondrial complex I electron transport inhibitors;

(22) Voltage-dependent sodium channel blockers;

(23) Inhibitors of acetyl CoA carboxylase;

(24) Mitochondrial complex IV electron transport inhibitors;

(25) Mitochondrial complex II electron transport inhibitors; and

(28) Ryanodine receptor modulators.

The phrase “MoA material group alpha” (hereafter “MoAMGA”) meanscollectively the following materials, abamectin, acephate, acequinocyl,acetamiprid, acrinathrin, alanycarb, aldicarb, allethrin,alpha-cypermethrin, aluminium phosphide, amitraz, azamethiphos,azinphos-ethyl, azinphos-methyl, azocyclotin, bendiocarb, benfuracarb,bensultap, beta-cyfluthrin, beta-cypermethrin, bifenthrin, bioallethrin,bioallethrin S-cyclopentenyl isomer, bioresmethrin, bistrifluron, borax,buprofezin, butocarboxim, butoxycarboxim, cadusafos, calcium phosphide,carbaryl, carbofuran, carbosulfan, cartap hydrochloride,chlorantraniliprole, chlordane, chlorethoxyfos, chiorfenapyr,chlorfenvinphos, chlorfluazuron, chiormephos, chloropicrin,chlorpyrifos, chlorpyrifos-methyl, chromafenozide, clofentezine,clothianidin, coumaphos, cyanide, cyanophos, cyantraniliprole,cycloprothrin, cyenopyrafen, cyflumetofen, cyfluthrin, cyhalothrin,cyhexatin, cypermethrin, cyphenothrin cyromazine, d-cis-trans-allethrin,DDT, deltamethrin, demeton-S-methyl, diafenthiuron, diazinon,dichlorvos/DDVP, dicrotophos, diflovidazin, diflubenzuron, dimethoate,dimethylvinphos, dinotefuran, disulfoton, DNOC, d-trans-allethrin,emamectin benzoate, empenthrin endosulfan, EPN, esfenvalerate,ethiofencarb, ethion, ethoprophos, etofenprox, etoxazole, famphur,fenamiphos, fenazaquin, fenbutatin oxide, fenitrothion, fenobucarb,fenoxycarb, fenpropathrin, fenpyroximate, fenthion, fenvalerate,flonicamid, fluacrypyrim, flubendiamide, flucycloxuron, flucythrinate,flufenoxuron, flumethrin, flupyradifurone, formetanate, fosthiazate,furathiocarb, gamma-cyhalothrin, halfenprox, halofenozide, heptenophos,hexaflumuron, hexythiazox, hydramethylnon, hydroprene, imicyafos,imidacloprid, imiprothrin, indoxacarb, isofenphos, isoprocarb,isoxathion, kadethrin, kinoprene, lambda-cyhalothrin, lepimectin,lufenuron, malathion, mecarbam, metaflumizone, methamidophos,methidathion, methiocarb, methomyl, methoprene,(methoxyaminothio-phosphoryl) salicylate, methoxychlor, methoxyfenozide,methyl bromide, metolcarb, mevinphos, milbemectin, monocrotophos, naled,nicotine, nitenpyram, novaluron, noviflumuron, oxamyl,oxydemeton-methyl, parathion, parathion-methyl, permethrin, phenothrin,phenthoate, phorate, phosalone, phosmet, phosphamidon, phosphine,phoxim, pirimicarb, pirimiphos-methyl, prallethrin, profenofos,propargite, propetamphos, propoxur, prothiofos, pymetrozine, pyraclofos,pyrethrin, pyridaben, pyridaphenthion, pyrimidifen, pyriproxyfen,quinalphos, resmethrin, rotenone, silafluofen, spinetoram, spinosad,spirodiclofen, spiromesifen, spirotetramat, sulfluramid, sulfotep,sulfoxaflor, sulfuryl fluoride, tartar emetic, tau-fluvalinate,tebufenozide, tebufenpyrad, tebupirimfos, teflubenzuron, tefluthrin,temephos, terbufos, tetrachlorvinphos, tetradifon, tetramethrin,tetramethrin, theta-cypermethrin, thiacloprid, thiamethoxam, thiocyclam,thiodicarb, thiofanox, thiometon, thiosultap-sodium, tolfenpyrad,tralomethrin, transfluthrin, triazarnate, triazophos, trichlorfon,triflumuron, trimethacarb, vamidothion, XMC, xylylcarb,zeta-cypermethrin, and zinc phosphide. For the avoidance of doubt, eachof the foregoing materials is an active ingredient.

The term “pest” means an organism that is detrimental to humans, orhuman concerns (such as, crops, food, livestock, etc.), where saidorganism is from Phyla Arthropoda, Mollusca, or Nematoda, particularexamples are ants, aphids, beetles, bristletails, cockroaches, crickets,earwigs, fleas, flies, grasshoppers, leafhoppers, lice (including sealice), locusts, mites, moths, nematodes, scales, symphylans, termites,thrips, ticks, wasps, and whiteflies, additional examples are pests in:

(1) Subphyla Chelicerata, Myriapoda, Crustacea, and Hexapoda;

(2) Classes of Arachnida, Maxillopoda, Symphyla, and Insecta;

(3) Order Anoplura. A non-exhaustive list of particular genera includes,but is not limited to, Haematopinus spp., Hoplopleura spp., Linognathusspp., Pediculus spp., and Polyplax spp. A non-exhaustive list ofparticular species includes, but is not limited to, Haematopinus asini,Haematopinus suis, Linognathus setosus, Linognathus ovillus, Pediculushumanus capitis, Pediculus humanus humanus, and Pthirus pubis.

(4) Order Coleoptera. A non-exhaustive list of particular generaincludes, but is not limited to, Acanthoscelides spp., Agriotes spp.,Anthonomus spp., Apion spp., Apogonia spp., Aulacophora spp., Bruchusspp., Cerosterna spp., Cerotoma spp., Ceutorhynchus spp., Chaetocnemaspp., Colaspis spp., Ctenicera spp., Curculio spp., Cyclocephala spp.,Diabrotica spp., Hypera spp., Ips spp., Lyctus spp., Megascel/s spp.,Meligethes spp., Otiorhynchus spp., Pantornorus spp., Phyllophaga spp.,Phyllotreta spp., Rhizotrogus spp., Rhynchites spp., Rhynchophorus spp.,Scolytus spp., Sphenophorus spp., Sitophilus spp., and Tribolium spp. Anon-exhaustive list of particular species includes, but is not limitedto, Acanthoscelides obtectus, Agrilus planipennis, Anoplophoraglabripennis, Anthonomus grandis, Ataenius spretulus, Atomaria linearis,Bothynoderes punctiventris, Bruchus pisorum, Callosobruchus maculatus,Carpophilus hemipterus, Cassida vittata, Cerotoma trifurcata,Ceutorhynchus assimilis, Ceutorhynchus napi, Conoderus scalaris,Conoderus stigmosus, Conotrachelus nenuphar, Cotinis nitida, Criocerisasparagi, Cryptolestes ferrugineus, Cryptolestes pusMus, Cryptolestesturcicus, Cylindrocopturus adspersus, Deporaus marginatus, Dermesteslardarius, Derrnestes maculatus, Epilachna varivestis, Faustinus cubae,Hylobius pales, Hypera postica, Hypothenemus hampei, Lasiodermaserricorne, Leptinotarsa decemlineata, Liogenys fuscus, Liogenyssuturalis, Lissorhoptrus oryzophilus, Maecolaspis joliveti, Melanotuscommunis, Meligethes aeneus, Melolontha melolontha, Oberea brevis,Qberea linearis, Oryctes rhinoceros, Oryzaephilus mercator, Oryzaephilussurinamensis, Oulema melanopus, Oulema oryzae, Phyllophaga cuyabana,Popillia japonica, Prostephanus truncatus, Rhyzopertha dominica Sitonalineatus, Sitophilus granarius, Sitophilus oryzae, Sitophilus zeamais,Stegobium paniceum, Tribolium castaneum, Tribolium confusum, Trogodermavariabile, and Zabrus tenebrioides.

(5) Order Dermaptera. A nonexhaustive list of particular speciesincludes, but is not limited to, Forficula auricularia.

(6) Order Blattaria. A non-exhaustive list of particular speciesincludes, but is not limited to, Blattella germanica, Blatta orientalis_(t) Parcoblatta pennsylvanica, Periplaneta americana, Periplanetaaustralasiae, Periplaneta brunnea, Periplaneta fuliginosa, Pycnoscelussurinamensis, and Supella longipalpa.

(7) Order Diptera. A non-exhaustive list of particular genera includes,but is not limited to, Aedes spp., Agromyza spp., Anastrepha spp.,Anopheles spp., Bactrocera spp., Ceratitis spp., Chrysops spp.,Cochliomyia spp., Contarinia spp., Culex spp., Dasineura spp., Deliaspp., Drosophila spp., Fannia spp., Hylemyia spp., Liriomyza spp., Muscaspp., Phorbia spp., Tabanus spp., and Tipula spp. A non-exhaustive listof particular species includes, but is not limited to, Agromyzafrontella, Anastrepha suspensa, Anastrepha ludens, Anastrepha obliqa,Bactrocera cucurbitae, Bactrocera dorsalis, Bactrocera invadens,Bactrocera zonata, Ceratitis capitata, Dasineura brassicae, Deliaplatura, Fannia canicularis, Fannia scalaris, Gasterophilusintestinalis, Gracillia perseae, Haematobia irritans, Hypodermalineatum, Liriomyza brassicae, Melophagus ovines, Musca autumnalis,Musca domestica, Oestrus ovis, Oscinella frit, Pegomya betae, Psilarosae, Rhagoletis cerasi, Rhagoletis pomonella, Rhagoletis mendax,Sitodiplosis mosellana, and Stomoxys calcitrans.

(8) Order Hemiptera. A non-exhaustive list of particular generaincludes, but is not limited to, Adelges spp., Aulacaspis spp.,Aphrophora spp., Aphis spp., Bemisia spp., Ceroplastes spp., Chionaspisspp., Chrysomphalus spp., Coccus spp., Empoasca spp., Lepidosaphes spp.,Lagynotomus spp., Lygus spp., Macrosiphum spp., Nephotettix spp., Nezaraspp., Philaenus spp., Phytocoris spp., Piezodorus spp., Planococcusspp., Pseudococcus spp., Rhopalosiphum spp., Saissetia spp., Therioaphisspp., Toumeyella spp., Toxoptera spp., Trialeurodes spp., Triatoma spp.and Unaspis spp. A non-exhaustive list of particular species includes,but is not limited to, Acrosternum hilare, Acyrthosiphon pisum,Aleyrodes pmletella, Aleurodicus disperses, Aleurothrixus floccosus,Amrasca biguttula biguttula, Aonidiella aurantil, Aphis gossypil, Aphisglycines, Aphis porni, Aulacorthum solani, Bemisia argentifolii, Bemisiatabaci, Blissus leucopterus, Brachycorynella asparagi, Brevennia rehi,Brevicoryne brassicae, Calocoris norvegicus, Ceroplastes rubens, Cimexhemipterus, Cimex lectularius, Dagbertus fasciatus, Dichelops furcatus,Diuraphis noxia, Diaphorina citri, Dysaphis plantaginea, Dysdercussuturellus, Edessa meditabunda, Eriosoma lanigerum, Eurygaster maura,Euschistus heros, Euschistus servus, Helopeltis antonii, Helopeltistheivora, Icerya purchasi, Idioscopus nitidulus, Laodelphax striatellus,Leptocorisa oratorius, Leptocorisa varicornis, Lygus hesperus,Maconellicoccus hirsutus, Macrosiphum euphorbiae, Macrosiphumgranariurn, Macrosiphum rosae, Macrosteles quadrilineatus, Mahanarvafrimbiolata, Metopolophium dirhodum, Mictis longicornis, Myzus persicae,Nephotettix cinctipes, Neumcolpus longirostris, Nezara viridula,Nilaparvata lugens, Parlatoria pergandii, Parlatoria ziziphi, Peregrinusmaidis, Phylloxera vitifoliae, Physokermes piceae, Phytocoriscalifornicus, Phytocoris relativus Piezodorus guildinii, Poecilocapsuslineatus, Psallus vaccinicola, Pseudacysta perseae, Pseudococcusbrevipes, Quadraspidiotus perniciosus, Rhopalosiphurn maidis,Rhopalosiphum padi, Saissetia oleae, Scaptocoris castanea, Schizaphisgraminurn, Sitobion avenae, Sogatella furcifera, Trialeurodesvaporariorum, Trialeurodes abutiloneus, Unaspis yanonensis, and Zuliaentrerriana.

(9) Order Hymenoptera. A non-exhaustive list of particular generaincludes, but is not limited to, Acromyrmex spp., Atta spp., Camponotusspp., Diprion spp., Formica spp., Monomorium spp., Neodiprion spp.,Pogonomyrmex spp., Polistes spp., Solenopsis spp., Vespula spp., andXylocopa spp. A non-exhaustive list of particular species includes, butis not limited to, Athalia rosae, Atta texana, Iridomyrmex humilis,Monomorium minimum, Monomorium pharaonis, Solenopsis invicta, Solenopsisgeminata, Solenopsis molesta, Solenopsis richtery, Solenopsis xyloni,and Tapinoma sessile.

(10) Order Isoptera. A non-exhaustive list of particular generaincludes, but is not limited to, Coptotermes spp., Cornitermes spp.,Cryptotermes spp., Heterotermes spp., Kalotermes spp., Incisitermesspp., Macrotermes spp., Marginitermes spp., Microcerotermes spp.,Procornitermes spp., Reticulitermes spp., Schedorhinotermes spp., andZootermopsis spp. A non-exhaustive list of particular species includes,but is not limited to, Coptotermes curvignathus, Coptotermes frenchi,Coptotermes formosanus, Heterotermes aureus, Microtermes obesi,Reticulitermes banyulensis, Reticulitermes grassei, Reticulitermesflavipes, Reticulitermes hageni, Reticulitermes hesperus, Reticulitermessantonensis Reticulitermes speratus, Reticulitermes tibialis, andReticulitermes virginicus.

(11) Order Lepidoptera. A non-exhaustive list of particular generaincludes, but is not limited to, Adoxophyes spp., Agrotis spp.,Argyrotaenia spp., Cacoecia spp., Caloptilia spp., Chilo spp.,Chrysodeixis spp., Collas spp., Crambus spp., Diaphania spp., Diatraeaspp., Earias spp., Ephestia spp., Epimecis spp., Feltia spp., Gortynaspp., Helicoverpa spp., Heliothis spp., Indarbela spp., Lithocolletisspp., Loxagrotis spp., Malacosoma spp., Peridroma spp., Phyllonorycterspp., Pseudaletia spp., Sesamia spp., Spodoptera spp., Synanthedon spp.,and Yponomeuta spp. A non-exhaustive list of particular speciesincludes, but is not limited to, Achaea janata, Adoxophyes orana,Agrotis Ipsilon, Alabama argillacea, Amorbia cuneana, Amyeloistransitella, Anacamptodes defectaria, Anarsia lineatella, Anomissabulifera, Anticarsia gemmatalis, Archips argyrospila, Archips rosana,Argyrotaenia citrana, Autographa gamma, Bonagota cranaodes, Borbocinnara, Bucculatrix thurberiella, Capua reticulana, Carposinaniponensis, Chlumetia transversa, Choristoneura rosaceana,Cnaphalocrocis medinalis, Conopomorpha cramerella, Cossus cossus, Cydiacaryana, Cydia funebrana, Cydia molesta, Cydia nigricana, Cydiapomonella, Darna diducta, Diatraea saccharalis, Diatraea grandiosella,Earias insulana, Earias vittella, Ecdytolopha aurantianurm Elasmopalpuslignosellus, Ephestia cautella, Ephestia elutella, Ephestia kuehniella,Epinotia aporema, Epiphyas postvittana, Erionota thrax, Eupoeciliaambiguella, Euxoa auxiliaris, Grapholita molesta, Hedylepta indicata,Helicoverpa armigera, Helicoverpa zea, Heliothis virescens, Hellulaundalis, Keiferia lycopersicella, Leucinodes orbonalis, Leucopteracoffeella, Leucoptera malifolielia, Lobesia botrana, Loxagrotisaibicosta, Lymantria dispar, Lyonetia clerkella, Mahasena corbetti,Mamestra brassicae, Maruca testulalis, Metisa plana, Mythimna unipuncta,Neoleucinodes elegantalis, Nymphula depunctalis, Operophtera brumata,Ostrinia nubilalis, Oxydia vesulia, Pandemis cerasana, Pandemisheparana, Papilio demodocus, Pectinophora gossypiella, Peridroma saucia,Perileucoptera coffeella, Phthorimaea operculella, Phyllocnistiscitrella, Pieris rapae, Plathypena scabra, Piodia interpunctella, Mutexylostella, Polychrosis viteana, Prays endocarpa, Prays oleae,Pseudaletia unipuncta, Pseudoplusia includens, Ra chiplusia nu,Scirpophaga incertulas, Sesamia inferens, Sesamia nonagrioides, Setoranitens, Sitotroga cerealella, Sparganothis pilleriana, Spodopteraexigua, Spodoptera frugiperda, Spodoptera eridania, Thecla basilides,Tineola bisselliella, Trichoplusia ni, Tuta absoluta, Zeuzera coffeae,and Zeuzera pyrina;

(12) Order Mallophaga. A non-exhaustive list of particular generaincludes, but is not limited to, Anaticola spp., Bovicola spp.,Chelopistes spp., Goniodes spp., Menacanthus spp., and Trichodectes spp.A non-exhaustive list of particular species includes, but is not limitedto, Bovicola bovis, Bovicola caprae, Bovicola avis, Chelopistesmeleagridis, Goniodes dissimilis, Goniodes gigas, Menacanthusstramineus, Menopon gallinae, and Trichodectes canis.

(13) Order Orthoptera. A non-exhaustive list of particular generaincludes, but is not limited to, Melanoplus spp., and Pterophylla spp. Anon-exhaustive list of particular species includes, but is not limitedto, Anabrus simplex, Gryllotalpa africana, Gryllotalpa australis,Gryllotalpa brachyptera, Gryllotalpa hexadactyla, Locusta migratoria,Microcentrum retinerve, Schistocerca gregaria, and Scudderia furcata.

(14) Order Siphonaptera. A non-exhaustive list of particular speciesincludes, but is not limited to, Ceratophyllus gallinae Ceratophyllusniger, Ctenocephalides canis, Ctenocephalides fells, and Pulex irritans.

(15) Order Siphonostomatoida. A non-exhaustive list of particularspecies includes, but is not limited to, Lepeophtheirus salmonis,Lepeophtheirus pectoralis, Caligus elongatus, and Caligus ciemensi.

(16) Order Thysanoptera. A non-exhaustive list of particular generaincludes, but is not limited to, Caliothrips spp., Frankliniella spp.,Scirtothrips spp., and Thrips spp. A non-exhaustive list of particularspecies includes, but is not limited to, Frankliniella fusca,Frankliniella occidentalis, Frankliniella schultzei, Frankliniellawilliamsi, Heliothrips haemorrhoidalis, Rhipiphorothrips cruentatus,Scirtothrips citri, Scirtothrips dorsalis, Taeniothripsrhopalantennalis, Thrips hawaiiensis, Thrips nigropilosus, Thripsorientalis, and Thrips tabaci.

(17) Order Thysanura. A non-exhaustive list of particular generaincludes, but is not limited to, Lepisma spp. and Thermobia spp..

(18) Order Acarina. A non-exhaustive list of particular genera includes,but is not limited to, Acarus spp., Aculops spp., Boophilus spp.,Demodex spp., Dermacentor spp., Epitrimerus spp., Eriophyes spp., Ixodesspp., Oligonychus spp., Panonychus spp., Rhizoglyphus spp., andTetranychus spp. A non-exhaustive list of particular species includes,but is not limited to, Acarapis woodi, Acarus sire, Aceria mangiferae,Aculops lycopersici, Aculus pelekassi, Aculus schlechtendali, Amblyommaamericanum, Brevipalpus obovatus, Brevipalpus phoenicis, Dermacentorvariabilis, Dermatophagoides pteronyssinus, Eotetranychus carpini,Notoedres cati, Oligonychus coffeae, Oligonychus ilicis, Panonychuscitri, Panonychus ulmi, Phyllocoptruta oleivora, Polyphagotarsonemuslatus, Rhipicephalus sanguineus, Sarcoptes scabiei, Tegolophusperseaflorae, Tetranychus urticae, and Varroa destructor.

(19) Order Symphyla. A non-exhaustive list of particular speciesincludes, but is not limited to, Scutigerella immaculate.

(20) Phylum Nematoda. A non-exhaustive list of particular generaincludes, but is not limited to, Aphelenchoides spp., Belonolaimus spp.,Criconemella spp., Ditylenchus spp., Heterodera spp., Hirschmanniellaspp., Hoplolairnus spp., Meloidogyne spp., Pratylenchus spp., andRadopholus spp. A non-exhaustive list of particular sp. includes, but isnot limited to, Dirofilaria immitis, Heterodera zeae, Meloidogyneincognita, Meloidogyne javanica, Onchocerca volvulus, Radopholussimilis, and Rotylenchulus reniformis.

The phrase “pesticidally effective amount” means the amount of apesticide needed to achieve an observable effect on a pest, for example,the effects of necrosis, death, retardation, prevention, removal,destruction, or otherwise diminishing the occurrence and/or activity ofa pest in a locus, this effect may come about when, pest populations arerepulsed from a locus, pests are incapacitated in, or around, a locus,and/or pests are exterminated in, or around, a locus. Of course, acombination of these effects can occur. Generally, pest populations,activity, or both are desirably reduced more than fifty percent,preferably more than 90 percent, and most preferably more than 99percent. In general a pesticidally effective amount, for agriculturalpurposes, is from about 0.0001 grams per hectare to about 5000 grams perhectare, preferably from about 0.0001 grams per hectare to about 500grams per hectare, and it is even more preferably from about 0.0001grams per hectare to about 50 grams per hectare.

DETAILED DESCRIPTION OF THE DISCLOSURE

This document discloses molecules of Formula One

wherein:

-   -   (A) R¹, R⁵, R⁶, R¹¹, and R¹² are each independently selected        from the group consisting of H, F, Cl, Br, I, CN, (C₁-C₆)alkyl,        (C₁-C₆)haloalkyl, (C₁-C₆)alkoxy, and (C₁-C₄)haloalkoxy;    -   (B) R², R³, and R⁴ are each independently selected from the        group consisting of H, F, Cl, Br, I, CN, (C₁-C₆)alkyl,        (C₂-C₆)alkenyl, (C₂-C₆)alkynyl, (C₁-C₆)haloalkyl, (C₁-C₆)alkoxy,        and (C₁-C₆)haloalkoxy;    -   (C) R⁷ is (C₁-C₆)haloalkyl;    -   (D) R⁹ is selected from the group consisting of (F), H, F, Cl,        Br, I, CN, (C₁-C₄)alkyl, (C₁-C₄)haloalkyl, (C₁-C₄)alkoxy, and        (C₁-C₄)haloalkoxy;    -   (E) R¹⁰ is selected from the group consisting of (F), F, Cl, Br,        I, CN, (C₁-C₆)alkyl, (C₂-C₆)alkenyl, (C₂-C₆)alkynyl,        (C₁-C₆)haloalkyl, (C₁-C₆)alkoxy, and (C₁-C₆)haloalkoxy;    -   (F) R⁹ and R¹⁰ together can optionally form a 3- to 5-membered        saturated or unsaturated, hydrocarbyl link,    -   wherein said hydrocarbyl link may optionally be substituted with        one or more substituents independently selected from the group        consisting of F, Cl, Br, I, CN, OH, and oxo;    -   (G) Q¹ and Q² are each independently O or S;    -   (H) R¹³ is selected from the group consisting of H,        (C₁-C₆)alkyl, (C₂-C₆)alkenyl, (C₁-C₆)haloalkyl, (C₁-C₆)alkoxy,        and (C₁-C₆)haloalkoxy;    -   (I) R¹⁴ is selected from the group consisting of (K), (O), H,        (C₁-C₄)alkyl, (C₂-C₆)alkenyl, (C₁-C₆)haloalkyl, (C₁-C₆)alkoxy,        and (C₁-C₆)haloalkoxy;    -   (J) R¹⁵ is selected from the group consisting of (K), H,        (C₁-C₆)alkyl, (C₂-C₆)alkenyl, (C₁-C₆)haloalkyl, (C₁-C₆)alkoxy,        and (C₁-C₆)haloalkoxy;    -   (K) R¹⁴ and R¹⁵ together can optionally form a 2- to 5-membered        saturated, hydrocarbyl link,    -   wherein said hydrocarbyl link may optionally be substituted with        one or more substituents independently selected from the group        consisting of F, Cl, Br, I, and CN;    -   (L) L is selected from the group consisting of        -   (1) a bond, and        -   (2) a (C₁-C₆)alkyl wherein said alkyl is optionally            substituted with one or more substituents independently            selected from the group consisting of F, Cl, CN, OH, and            oxo;    -   (M) X is selected from the group consisting of        -   (1) R¹⁷, and        -   (2) a NR¹⁶R¹⁷,        -   (3) OR¹⁷, and        -   (4) SR¹⁷;    -   (N) R⁶ is selected from the group consisting of (O), (Q), H,        (C₁-C₆)alkyl, (C₂-C₆)alkenyl, (C₁-C₆)haloalkyl, (C₁-C₆)alkoxy,        (C₂-C₆)alkenyloxy, (C₁-C₆)haloalkoxy, amino, and        NHC(O)O(C₁-C₆)alkyl;    -   (O) R¹⁴ and R¹⁶ together can optionally form a 2- to 4-membered        saturated link that is either (1) a hydrocarbyl link or (2) a        heterohydrocarbyl link that contains one or more heteroatoms        selected from the group consisting of nitrogen, sulfur, and        oxygen,        -   wherein said link may optionally be substituted with one or            more substituents independently selected from the group            consisting of F, Cl, Br, I, CN, OH, and oxo;    -   (P) R¹⁷ is selected from the group consisting of (Q), H,        (C₁-C₆)alkyl, (C₂-C₆)alkenyl, (C₂-C₆)alkynyl, (C₁-C₆)haloalkyl,        (C₂-C₆)haloalkenyl, (C₃-C₆)halocycloalkyl, (C₁-C₆)alkoxy,        (C₃-C₆)cycloalkyl, (C₂-C₆)alkenyloxy, (C₁-C₆)haloalkoxy, and        (C₁-C₆)alkyl(C₃-C₆)cycloalkyl;    -   (Q) R¹⁶ and R¹⁷ together can optionally form a 2- to 6-membered        saturated link that is either (1) a hydrocarbyl link or (2) a        heterohydrocarbyl link that contains one or more heteroatoms        selected from the group consisting of nitrogen, sulfur, and        oxygen,        -   wherein said link may optionally be substituted with one or            more substituents independently selected from the group            consisting of F, Cl, Br, I, CN, OH, and oxo; and        -   agriculturally acceptable add addition salts, salt            derivatives, solvates, ester derivatives, crystal            polymorphs, isotopes, resolved stereoisomers, and tautomers,            of the molecules of Formula One.

In another embodiment R¹, R³, R⁴, R⁵, R⁶, R⁹, R¹¹, R¹², R¹³, R¹⁴ R¹⁵,R¹⁶, and R¹⁷ are H. This embodiment may be used in combination with theother embodiments of R², R⁷, R¹⁰, Q¹, L, Q², and X.

In another embodiment R² is F, Cl, Br, or CH₃. This embodiment may beused in combination with the other embodiments of R¹, R³, R⁴, R⁵, R⁶,R⁷, R⁹, R¹⁰, R¹¹, R¹², Q¹, R¹³, R¹⁴, R¹⁵, L, Q², X, R¹⁶, and R¹⁷.

In another embodiment R³ is F, Cl, Br, or CH═CH₂. This embodiment may beused in combination with the other embodiments of R¹, R², R⁴, R⁵, R⁶,R⁷, R⁹, R¹⁰, R¹¹, R¹², Q¹, R¹⁴, L, Q², X, R¹⁶, and R¹⁷.

In another embodiment R⁴ is Cl, Br, or CH₃. This embodiment may be usedin combination with the other embodiments of R¹, R², R³, R⁵, R⁶, R⁷, R⁹,R¹⁰, R¹¹, R¹², Q¹, R¹³, R¹⁴, R¹⁵, L, Q², X, R¹⁶, and R¹⁷.

In another embodiment R², R³, and R⁴ are Cl. This embodiment may be usedin combination with the other embodiments of R¹, R⁵, R⁶, R⁷, R⁹, R¹⁰,R¹¹, R¹², Q¹, R¹³, R¹⁴, L, Q², X, R¹⁶, and R¹⁷.

In another embodiment R⁷ is (C₁-C₆)haloalkyl. This embodiment may beused in combination with the other embodiments of R¹, R², R³, R⁴, R⁵,R⁶, R⁹, R¹⁰, R¹¹, R¹², Q¹, R¹³, R¹⁴, R¹⁵, L, Q², X, R¹⁶, and R¹⁷.

In another embodiment R⁷ is CF₃, CF₂CH₃, or CF₂CH₂CH₃. This embodimentmay be used in combination with the other embodiments of R¹, R², R³, R⁴,R⁵, R⁶, R⁹, R¹⁰, R¹¹, Q¹, R¹³, R¹⁴, L, Q², X, and R¹⁷.

In another embodiment R¹⁰ is Cl, Br, I, CH₃, or CF₃. This embodiment maybe used in combination with the other embodiments of R¹, R², R³, R⁴, R⁵,R⁶, R⁹, R¹¹, R¹², Q¹, R¹³, R¹⁴, R¹⁶, L, Q², X, R¹⁶, and R¹⁷.

In another embodiment Q¹ and Q² are O. This embodiment may be used incombination with the other embodiments of R¹, R², R³, R⁴, R⁵, R⁶, R⁷,R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R¹⁵, L, X, R¹⁶, and R¹⁷.

In another embodiment R¹³, R¹⁴, and R¹⁵ are CH₃ or CH₂CH₃. Thisembodiment may be used in combination with the other embodiments of R¹,R², R³, R⁴, R⁵, R⁶, R⁷, R⁹, R¹⁰, R¹¹, R¹², Q¹, L, Q², X, R¹⁶, and R¹⁷.

In another embodiment R¹⁴ and R¹⁵ together form a 2-membered saturated,hydrocarbyl link. This embodiment may be used in combination with theother embodiments of R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁹, R¹⁰, R¹¹, R¹², Q¹,R¹³, L, Q², X, R¹⁶, and R¹⁷.

In another embodiment L is a bond. This embodiment may be used incombination with the other embodiments of R¹, R², R³, R⁴, R⁵, R⁶, R⁷,R¹¹, R¹⁰, R¹¹, R¹², Q¹, R¹³, R¹⁴, R¹⁵, Q², X, R¹, and R¹⁷.

In another embodiment X is R¹⁷. This embodiment may be used incombination with the other embodiments of R¹, R², R³, R⁴, R⁵, R⁶, R⁷,R¹¹, R¹⁰, R¹¹, R¹², Q¹, R¹³, R¹⁴, R¹⁵, L, and Q².

In another embodiment X is NR¹⁶R¹⁷. This embodiment may be used incombination with the other embodiments of R¹, R², R³, R⁴, R⁵, R⁶, R⁷,R⁹, R¹⁰, R¹¹, R¹², Q¹, R¹³, R¹⁴, R¹⁵, L, and Q².

In another embodiment R¹⁶ is CH₃, CH₂CH₃, OCH₃, OCH₂CH═CH₂, NH₂, orNHC(O)OC(CH₃)₃. This embodiment may be used in combination with theother embodiments of R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁹, R¹⁰, R¹¹, R¹², Q¹,R¹³, R¹⁴, R¹⁵, L, Q², X, and R¹⁷.

In another embodiment R¹⁴ and R¹⁵ together form a 2- to 4-memberedsaturated link that is either (1) a hydrocarbyl link or (2) aheterohydrocarbyl link that contains one or more oxygen atoms. Thisembodiment may be used in combination with the other embodiments of R¹,R², R³, R⁴, R⁵, R⁶, R⁷, R⁹, R¹⁰, R¹, R¹², Q¹, R¹³, R¹⁵, L, Q², X, andR¹⁷.

In another embodiment R¹⁷ is CH₂CH₃, CH₂CH₂CH₂CH₃, CH₂CH₂CH(CH₃)₂,CH₂CH═CH₂, CH₂C≡CH, CH₂CHF₂, CH₂CF₃, CH₂CH₂CF₃, CH₂CF₂CH₃, CH(CH₃)CF₃,CH₂CH₂CH₂CF₃, CH═CHCH₂CF₃, 3,3-difluorocyclobutyl, CH₂CH₂ cyclopropyl,and CH₂ cyclobutyl. This embodiment may be used in combination with theother embodiments of R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁹, R¹⁰, R¹¹, R¹², Q¹,R¹³, R¹⁴, R¹⁵, L, Q², X, and R¹⁶.

In another embodiment:

-   -   (A) R¹, R⁵, R⁶, R¹¹, and R¹² are H;    -   (B) R², R³, and R⁴ are each independently selected from the        group consisting of H, F, Cl, Br, (C₁-C₆)alkyl, and        (C₂-C₆)alkenyl;    -   (C) R⁷ is (C₁-C₆)haloalkyl;    -   (D) R⁹ is H;    -   (E) R¹⁰ is selected from the group consisting of Cl, Br, I,        (C₁-C₆)alkyl, and (C₁-C₆)haloalkyl;    -   (G) Q¹ and Q² are O;    -   (H) R¹³ is selected from the group consisting of H and        (C₁-C₆)alkyl;    -   (I) R¹⁴ is selected from the group consisting of (K), (O), H,        and (C₁-C₄)alkyl;    -   (J) R¹⁵ is selected from the group consisting of (K), H, and        (C₁-C₆)alkyl;    -   (K) R¹⁴ and R¹⁵ together can optionally form a 2- to 5-membered        saturated, hydrocarbyl link;    -   (L) L is a bond;    -   (M) X is selected from the group consisting of        -   (1) R¹⁷, and        -   (2) a NR¹⁶R¹⁷;    -   (N) R¹⁶ is selected from the group consisting of (O), H,        (C₁-C₆)alkyl, (C₁-C₆)alkoxy, (C₂-C₆)alkenyloxy, amino, and        NHC(O)O(C₁-C₆)alkyl;    -   (O) R¹⁴ and R¹⁶ together can optionally form a 2- to 4-membered        saturated, link that is either (1) a hydrocarbyl link or (2) a        heterohydrocarbyl link that contains one or more oxygen atoms;    -   (P) R¹⁷ is selected from the group consisting of H,        (C₁-C₆)alkyl, (C₂-C₆)alkenyl, (C₂-C₆)alkynyl, (C₁-C₆)haloalkyl,        (C₂-C₆)haloalkenyl, (C₃-C₆)halocycloalkyl, and        (C₁-C₆)alkyl(C₃-C₆)cycloalkyl.

Preparation of Benzyl Halides

Benzyl alcohol 1-3, wherein R¹, R², R³, R⁴, R⁵, R⁶, and R⁷ are aspreviously disclosed, may be prepared in several ways. Ketones 1-1 maybe prepared by treating bromobenzenes with a lithium base such asn-butyllithium in a polar, aprotic solvent preferably diethyl ether attemperatures from about −78° C. to about 0° C. followed by treatmentwith esters R⁷C(O)O(C₁-C₄)alkyl, wherein R⁷ is as previously disclosed,such as ethyl 2,2-difluoropropanoate (not shown). Treatment of ketones1-1, wherein R¹, R², R³, R⁴, R⁵, and R⁷ are as previously disclosed,with a reducing agent such as sodium borohydride, in the presence of abase, such as aqueous sodium hydroxide, in a polar, protic solventpreferably methanol at about −10° C. to about 10° C. may provide benzylalcohols 1-3 (Scheme 1, step a). Alternatively, aldehydes 1-2, whereinR⁶ is H and R¹, R², R³, R⁴, and R⁵ are as previously disclosed, may beallowed to react with trifluorotrimethylsilane in the presence of acatalytic amount of tetrabutylammonium fluoride in a polar, aproticsolvent preferably tetrahydrofuran (Scheme 1, step b) to provide benzylalcohols 1-3, wherein R⁷ is CF₃. Subsequently, benzyl alcohols 1-3 maybe converted into benzyl halides 1-4, wherein E is Br, Cl, or I, and R¹,R², R³, R⁴, R⁵, R⁶, and R⁷ are as previously disclosed, by treatmentwith a halogenating reagent, such as N-bromosuccinimide, andtriethylphosphite in a solvent that does not react with the reagentspreferably dichloromethane at about 40° C. to provide benzyl halides1-4, E is Br (Scheme 1, step c). Alternatively, benzyl alcohols 1-3 maybe converted into benzyl halides 1-4, where E is Br by treatment with asulfonyl chloride such as methanesulfonyl chloride in the presence of abase such as triethylamine and subsequent treatment of the resultantsulfonate with a transition metal bromide such as iron(III) bromide.Additionally, treatment with chlorinating reagents such as thionylchloride in the presence of a base such as pyridine in a hydrocarbonsolvent such as toluene at about 110° C. may provide benzyl halides 1-4,where E is Cl (Scheme 1, step c).

Preparation of Fluorinated Vinylbenzoic Esters and Acids

Halobenzoic acids 2-1, wherein R⁹, R¹⁰, R¹¹, and R¹² are as previouslydisclosed may be converted to halobenzoic acid esters 2-2, wherein R⁹,R¹⁰, R¹¹, and R¹² are as previously disclosed. Halobenzoic acids 2-1,may be treated with an acid, such as sulfuric acid, in the presence of a(C₁-C₈)alcohol such as ethanol, to provide halobenzoic acid ethyl esters2-2 (Scheme 2, step a). Fluorinated vinylbenzoic acid esters 2-3 may beaccessed via reaction of 2-2 with a fluorinated vinyl silane in thepresence of a palladium catalyst such astetrakis(triphenylphospine)palladium(0), a copper additive such ascopper(I) iodide, and a fluoride source, such as cesium fluoride in apolar, aprotic solvent preferably 1,3-dimethyl-2-imidazolidinone attemperatures ranging from about ambient temperature to about 45° C., toprovide fluorinated vinyl benzoic acid esters 2-3 (Scheme 2, step b).Fluorinated vinyl benzoic acid esters 2-3 may be treated with a metalhydroxide source such as lithium hydroxide in a mixed solvent systemcomprising a polar, aprotic solvent preferably tetrahydrofuran andpolar, protic solvents preferably methanol and water at about ambienttemperature to provide fluorinated vinyl benzoic acids 2-4 (Scheme 2,step c).

Alternatively, halobenzoic acids 2-1 may be directly treated with avinyl borane source such as vinyltrifluoroborate or3-hydroxy-2,3-dimethylbutan-2-yl hydrogen vinylboronate in the presenceof a palladium catalyst such as 1,1′-bis(diphenylphosphino)ferrocenepalladium(II) dichloride, and a base such as potassium carbonate, in apolar, aprotic solvent preferably dimethylsulfoxide at temperaturesranging from about 80° C. to about 140° C., to provide vinyl benzoicacids 3-1, wherein R¹, R¹⁰, R¹¹, and R¹² are as previously disclosed(Scheme 3, step a). Vinyl benzoic acids 3-1 may be treated with brominesource such as N-bromosuccinimide, and a fluorine source such astriethylamine trihydrofluoride, in a polar, aprotic solvent preferablydichloromethane at about 0° C., to provide bromofluoroalkyl benzoicacids 3-2, wherein R⁹, R¹⁰, R¹¹, and R¹² are as previously disclosed(Scheme 3, step b). Bromofluoroalkyl benzoic acids 3-2 may be treatedwith a base such as potassium tert-butoxide, in a polar, protic solventpreferably methanol, at temperatures ranging from about 0° C. to aboutambient temperature, to provide fluorinated vinyl benzoic acids 2-4(Scheme 3, step c).

Preparation of Fluorinated Phenyl Allylbenzoic Acids

Benzyl halides 1-4 and fluorinated vinylbenzoic acids 2-4 may be treatedwith a copper(I) source such as copper(I) chloride or copper(I) bromideand a pyridine ligand such as 2,2-bipyridyl in a polar, aprotic solventpreferably N-methyl-2-pyrrolidone, at a temperature between about 100°C. to about 180° C. to provide fluorinated phenyl allylbenzoic acids4-1, wherein R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁹, R¹⁰, R¹¹, and R¹² are aspreviously disclosed (Scheme 4, step a).

Preparation of Fluorinated Phenyl Allylbenzoic Amides

Fluorinated phenyl allylbenzoic amides 5-3, wherein Q¹ is O and R¹, R²,R³, R⁴, R⁵, R⁶, R⁷, R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R¹, L, Q², and X are aspreviously disclosed may be prepared by treatment with amines or aminesalts 5-2, wherein R¹³, R¹⁴, R¹⁵, L, Q², and X are as previouslydisclosed, and activated carboxylic acids 5-1, wherein A is anactivating group, and R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁹, R¹⁰, R¹¹, and R¹²are as previously disclosed, with a base such as triethylamine,diisopropylethylamine, or 4-methylmorpholine in a polar, aprotic solventsuch as dichloromethane, tetrahydrofuran, 1,2-dichloroethane,N,N-dimethylformamide, or any combination thereof, at temperaturesbetween about 0° C. and about 120° C. (Scheme 5, step a).

Activated carboxylic acids 5-1 may be an acid halide such as an acidchloride, an acid bromide, or an acid fluoride; a carboxylic ester suchas a para-nitrophenyl ester, a pentafluorophenyl ester, an ethyl(hydroxyiminio)cyanoacetate ester, a methyl ester, an ethyl ester, abenzyl ester, an N-hydroxysuccinimidyl ester, a hydroxybenzotriazol-1-ylester, or a hydroxypyridyltriazol-1-yl ester; an O-acylisourea; an acidanhydride; or a thioester. Acid chlorides may be prepared from thecorresponding carboxylic acids by treatment with a dehydrating,chlorinating reagent such as oxalyl chloride or thionyl chloride.Activated carboxylic acids 5-1 may be prepared from carboxylic acids insitu with a uronium salt such as1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium3-oxid hexafluorophosphate (HATU),O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate(HBTU), or(1-cyano-2-ethoxy-2-oxoethylidenaminooxy)dimethylamino-morpholino-carbeniumhexafluorophosphate (COMU). Activated carboxylic acids 5-1 may also beprepared from carboxylic acids in situ with a phosphonium salt such asbenzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate(PyBop). Activated carboxylic acids 5-1 may also be prepared fromcarboxylic acids in situ with a coupling reagent such as1-(3-dimethylamino propyl)-3-ethylcarbodiimide, ordicyclohexylcarbodiimide in the presence of a triazole such ashydroxybenzotriazole-monohydrate (HOBt) or 1-hydroxy-7-azabenzotriazole(HOAt). O-Acylisoureas may be prepared with a dehydrating carbodimidesuch as 1-(3-dimethylamino propyl)-3-ethylcarbodiimide ordicyclohexylcarbodiimide. Activated carboxylic acids 5-1 may also beprepared from carboxylic acids in situ with a coupling reagent such as2-chloro-1,3-dimethylimidazolidinium hexafluorophosphate (CIP) in thepresence of a triazole such as 1-hydroxy-7-azabenzotriazole (HOAt).

Amines or amine salts 5-2 may be generated in situ from thecorresponding N-tert-butoxycarbonyl amines by treatment with an acidsuch as hydrogen chloride. Optionally, the amine salts 5-2 may beneutralized in the presence of a base such as sodium bicarbonate ortriethylamine prior to reaction with activated carboxylic acids 5-1 orin situ during reaction with activated carboxylic acids 5-1 to providefluorinated phenyl allylbenzoic amides 5-3.

Fluorinated phenyl allylbenzoic amides 6-1, wherein R¹, R², R³, R⁴, R⁵,R⁶, R⁷, R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R¹⁵, Q¹, L, Q², and X are aspreviously disclosed may be exposed to ultraviolet irradiation indeuterated or non-deuterated polar, aprotic solvents such as acetone toprovide (E)-fluorinated phenyl allylbenzoic amides 6-2, wherein R¹, R²,R³, R⁴, R⁵, R⁶, R⁷, R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R¹⁵, Q¹, L, Q², and Xare as previously disclosed (Scheme 6, step a).

Activated carboxylic acids 5-1 may be treated with amino acids 7-1,wherein R¹³ is H, L is a bond, and R¹⁴ and R¹⁵ are as previouslydisclosed, and a base such as triethylamine, diisopropylethylamine, or4-methylmorpholine (Scheme 7, step 7a), followed by treatment with adehydration reagent such as trifluoroacetic anhydride, in a polar,aprotic solvent such as dichloromethane, tetrahydrofuran,1,2-dichloroethane, N,N-dimethylformamide, or any combination thereof,at temperatures between about 0° C. and about 120° C., to provideazlactone 7-2, wherein L is a bond, and R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁹,R¹⁰, R¹¹, R¹², R¹⁴, and R¹⁵ are as previously disclosed (Scheme 7, stepb).

Azlactone 7-2 may be treated with a nucleophile 7-3, wherein X is aspreviously disclosed, and a base such as triethylamine,diisopropylethylamine, or 4-methylmorpholine, in a polar, aproticsolvent such as dichloromethane, at temperatures between about 0° C. andabout 120° C., to give fluorinated phenyl allylbenzoic amides 7-4,wherein R¹³ is H, L is a bond, Q¹ and Q² are O, and R¹, R², R³, R⁴, R⁵,R⁶, R⁷, R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R¹⁵, and X are as previouslydisclosed (Scheme 7, step c).

Alternatively, activated carboxylic acids 5-1 may be treated with aminoacids 8-1, wherein R¹³ is H, and L, R¹⁴, and R¹⁵ are as previouslydisclosed, and a base such as triethylamine, diisopropylethylamine, or4-methylmorpholine (Scheme 8, step a), followed with a thionating agentsuch as Lawesson's reagent to provide thioamide 8-2, wherein Q¹ is S,R¹³ is H, and R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁹, R¹⁰, R¹, R¹², R¹⁴, R¹⁵, L,and Q² are as previously disclosed (Scheme 8, step b).

Thioamide 8-2 may be treated with a nucleophile 7-3, wherein X is aspreviously disclosed, and a base such as triethylamine,diisopropylethylamine, or 4-methylmorpholine, in a polar, aproticsolvent such as dichloromethane, at temperatures between about 0° C. andabout 120° C., to give fluorinated phenyl allylbenzoic amides 8-3,wherein Q¹ is S, R¹³ is H, and R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁹, R¹⁰, R¹¹,R¹², R¹³, R¹⁴, R¹⁵, L, Q², and X are as previously disclosed (Scheme 8,step c).

Preparation of Amines and Amine Salts 5-2

Amino acids 8-1 may be treated with di-tert-butyl dicarbonate and abase, such as triethylamine, in a polar, aprotic solvent preferablydichloromethane, at temperatures between about 0° C. and about 120° C.,to give carbamate acids 9-2, wherein R¹³ is H and L, R¹⁴, and R¹⁵ are aspreviously disclosed (Scheme 9, step a). Activated carbamate acids 9-2may be treated with a nucleophile 7-3 and a base such as triethylamine,diisopropylethylamine, or 4-methylmorpholine, in a polar, aproticsolvent preferably dichloromethane, at temperatures between about 0° C.and about 120° C., to give carbamates 9-3 (Scheme 9, step b). Activatedcarbamate acids 9-2 may be a carbamate ester prepared in situ with acoupling reagent such as 1-(3-dimethylamino propyl)-3-ethylcarbodiimide,or dicyclohexylcarbodiimide in the presence of a triazole such ashydroxybenzotriazole-monohydrate (HOBt) or 1-hydroxy-7-azabenzotriazole(HOAt). O-Acylisoureas may be prepared with a dehydrating carbodimidesuch as 1-(3-dimethylamino propyl)-3-ethylcarbodiimide ordicyclohexylcarbodiimide. Carbamate esters may also be prepared fromcarboxylic acids in situ with a coupling reagent such as2-chloro-1,3-dimethylimidazolidinium hexafluorophosphate (CIP) in thepresence of a triazole such as 1-hydroxy-7-azabenzotriazole (HOAt).Carbamates 9-3 may be treated with an alkylating agent 9-4, wherein LGis a leaving group selected from mesylate, tosylate, triflate, halide,and carboxylate, and R¹³ is as previously disclosed, and a base such assodium hydride or cesium carbonate, in a polar, aprotic solvent such asdiethyl ether, tetrahydrofuran, or dioxane, at temperatures betweenabout 0° C. and about 120° C., to give carbamates 9-5, wherein R¹³ isnot H, and R¹³, R¹⁴ and R¹⁵ are as previously disclosed (Scheme 9, stepe).

Carbamates 9-3 and 9-5 may be treated with an acid such as hydrochloricacid, in a polar, aprotic solvent preferably dichloromethane, attemperatures between about 0° C. and about 120° C., to give amine salts5-2, wherein Q² is O (Scheme 9, step c). Amine salts 5-2 may beneutralized in the presence of a base such as sodium bicarbonate ortriethylamine. Alternatively, carbamates 9-3 and 9-5 may be treated witha thionating agent such as Lawesson's reagent (Scheme 9, step d), priorto the acid promoted deprotection, to give amine salts 5-2, wherein Q²is S (Scheme 9, step c).

EXAMPLES

These examples are for illustration purposes and are not to be construedas limiting this disclosure to only the embodiments disclosed in theseexamples.

Starting materials, reagents, and solvents that were obtained fromcommercial sources were used without further purification. Anhydroussolvents were purchased as Sure/Seal™ from Aldrich and were used asreceived. Melting points were obtained on a Thomas Hoover Unimeltcapillary melting point apparatus or an OptiMelt Automated Melting PointSystem from Stanford Research Systems and are uncorrected. Examplesusing “room temperature” were conducted in climate controlledlaboratories with temperatures ranging from about 20° C. to about 24° C.Molecules are given their known names, named according to namingprograms within ISIS Draw, ChemDraw, or ACD Name Pro. If such programsare unable to name a molecule, such molecule is named using conventionalnaming rules. ¹H NMR spectral data are in ppm (δ) and were recorded at300, 400, 500, or 600 MHz; ¹³C NMR spectral data are in ppm (δ) and wererecorded at 75, 100, or 150 MHz, and ¹⁹F NMR spectral data are in ppm(δ) and were recorded at 376 MHz, unless otherwise stated.

Example 1: Preparation of(Z)-2-bromo-4-(1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzoicacid (C1)

To a 25 mL round-bottomed flask were added 2,2′-bipyridine (0.255 g,1.63 mmol), 2-bromo-4-(1-fluorovinyl)benzoic acid (C24) (1.00 g, 4.08mmol), and 5-(1-bromo-2,2,2-trifluoroethyl)-1,2,3-trichlorobenzene (2.79g, 8.16 mmol) in N-methylpyrrolidone (2.0 mL) to give a yellow solution.Copper(I) bromide (0.117 g, 0.816 mmol) was added and the reactionmixture was purged with nitrogen for 5 minutes. The reaction was thenheated to 150° C. for 3 hours. The reaction mixture was poured into icewater (100 mL). The water was filtered and the resultant black gum wasdissolved in ethyl acetate (800 mL), washed with brine (2×200 mL), andwater (2×200 mL), dried over magnesium sulfate, filtered, andconcentrated to provide the title compound as a brown oil (1.40 g, 64%):¹H NMR (400 MHz, CDCl₃) δ 8.03 (d, J=8.2 Hz, 1H), 7.89 (d, J=1.8 Hz,1H), 7.59 (dd, J=8.3, 1.8 Hz, 1H), 7.43 (s, 2H), 5.83 (dd, J=32.4, 9.6Hz, 1H), 4.60 (p, J=8.8 Hz, 1H); ¹⁹F NMR (376 MHz, CDCl₃) δ −69.32 (d,J=2.3 Hz), −108.70-−119.01 (m); ESIMS m/z 505 ([M−H]⁻).

The following compounds were prepared in like manner to the procedureoutlined in Example 1:

(Z)-4-(1,4,4,4-Tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzoicacid (C2)

Isolated as a yellow oil (7.6 g, 68%): ¹H NMR (400 MHz, CDCl₃) δ 8.04(d, J=8.2 Hz, 1H), 7.99-7.94 (m, 1H), 7.84 (dd, J=8.2, 1.8 Hz, 1H), 7.44(s, 2H), 5.90 (dd, J=32.4, 9.6 Hz, 1H), 4.62 (p, J=8.9 Hz, 1H); ¹⁹F NMR(376 MHz, CDCl₃) δ −59.60, −69.28 (d, J=2.3 Hz), −112.11; ESIMS m/z 493([M−H]⁻).

(Z)-4-(1,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)pent-1-en-1-yl)-2-(trifluoromethyl)benzoicacid (C3)

Isolated as a yellow foam (0.628 g, 60%): ¹H NMR (400 MHz, CDCl₃) δ 8.00(d, J=8.2 Hz, 1H), 7.95 (d, J=8.8 Hz, 1H), 7.81 (d, J=8.3 Hz, 1H), 7.42(s, 2H), 5.96 (dd, J=33.6, 9.8 Hz, 1H), 4.29 (td, J=14.3, 9.8 Hz, 1H),1.65 (t, J=18.4 Hz, 3H); ¹⁹F NMR (376 MHz, CDCl₃) δ −59.61,−92.97-−97.35 (m), −114.82; ESIMS m/z 491 ([M−H]⁻).

(Z)-2-Chloro-4-(1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzoicacid (C4)

Isolated as a white solid (4.27 g, 88%): ¹H NMR (400 MHz, CDCl₃) δ 8.07(d, J=8.2 Hz, 1H), 7.68 (d, J=1.7 Hz, 1H), 7.54 (dd, J=8.3, 1.8 Hz, 1H),7.43 (s, 2H), 5.85 (dd, J=32.4, 9.6 Hz, 1H), 4.60 (p, J=8.8 Hz, 1H); ¹⁹FNMR (376 MHz, CDCl₃) δ −69.33 (d, J=2.2 Hz), −112.18 (d, J=2.4 Hz);ESIMS m/z 461 ([M−H]⁻).

(Z)-4-(3-(3,5-Dibromo-4-chlorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-2-(trifluoromethyl)benzoicacid (C5)

Isolated as a brown gum (2.00 g, 37%): ESIMS m/z 583 ([M−H]⁻).

(Z)-4-(3-(3,5-Dichlorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-2-(trifluoromethyl)benzoicacid (C6)

Isolated as a brown gum (0.50 g, 43%): ¹H NMR (400 MHz, DMSO-d₆) δ 13.9(br s, 1H), 8.16 (s, 1H), 8.09 (d, J=8.0 Hz, 1H), 7.92 (d, J=8.0 Hz,1H), 7.82 (s, 2H), 7.64 (t, J=6.0 Hz, 1H), 6.90 (dd, J=36.0, 10.4 Hz,1H), 5.26-5.17 (m, 1H); IR (thin film) 3416, 2926, 1716, 1119 cm⁻¹;ESIMS m/z 449 ([M+H]⁺).

(Z)-4-(3-(3,4-Dichlorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-2-(trifluoromethyl)benzoicacid (C7)

Isolated as a brown gum (2.50 g, 56%): ¹H NMR (300 MHz, DMSO-d₆) δ 13.9(br s, 1H), 8.16 (s, 1H), 8.09 (d, J=10.8 Hz, 1H), 8.08 (s, 1H), 7.92(d, J=8.1 Hz, 1H), 7.75-7.65 (m, 2H), 6.90 (dd, J=36.0, 10.4 Hz, 1H),5.22-5.16 (m, 1H); IR (thin film) 3440, 2927, 1716, 1175 cm⁻¹; ESIMS m/z459 ([M−H]⁻).

(Z)-4-(3-(3,5-Dibromophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-2-(trifluoromethyl)benzoicacid (C8)

Isolated as a brown gum (2.20 g, 39%): ¹H NMR (300 MHz, CDCl₃) δ8.05-7.95 (m, 2H), 7.84 (d, J=7.2 Hz, 1H), 7.69-7.68 (m, 1H), 7.49 (s,2H), 5.95 (dd, J=32.7, 9.6 Hz, 1H), 4.64-4.58 (p, 1H); IR (thin film)3439, 2925, 1714, 1118, 746 cm⁻¹; ESIMS m/z 549 ([M−H]⁻).

(Z)-4-(3-(3,5-Dichloro-4-fluorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-2-(trifluoromethyl)benzoicacid (C9)

Isolated as a brown gum (1.20 g, 54%): ¹H NMR (300 MHz, CDCl₃) δ 7.88(s, 2H), 7.76-7.75 (m, 1H), 7.37 (d, J=6.0 Hz, 2H), 5.90 (dd, J=32.1,9.0 Hz, 1H), 4.62-4.56 (p, 1H); IR (thin film) 3445, 2926, 1698, 1260,750 cm⁻¹; ESIMS m/z 477 ([M−H]⁻).

(Z)-4-(3-(4-Chloro-3,5-dimethylphenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-2-(trifluoromethyl)benzoicacid (C10)

Isolated as a yellow gum (2.20 g, 53%): ¹H NMR (300 MHz, CDCl₃) δ 8.01(d, J=8.1 Hz, 1H), 7.94 (s, 1H), 7.83 (d, J=8.1 Hz, 1H), 7.11 (s, 2H),6.00 (dd, J=33.0, 9.9 Hz, 1H), 4.58-4.55 (m, 1H), 2.40 (s, 6H); IR (thinfilm) 3445, 1713, 852 cm⁻¹; ESIMS m/z 453 ([M−H]⁻).

(Z)-4-(3-(4-Bromo-3,5-dichlorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-2-(trifluoromethyl)benzoicacid (C11)

Isolated as a brown solid (1.50 g, 65%): mp 78-81° C.; ¹H NMR (300 MHz,CDCl₃) δ 8.09-7.99 (m, 2H), 7.83-7.81 (m, 1H), 7.42 (s, 2H), 5.95 (dd,J=32.4 Hz, 9.6 Hz, 1H), 4.63-4.57 (m, 1H); IR (thin film) 3445, 1713,852 cm⁻¹; ESIMS m/z 538 ([M+H]⁺).

(Z)-4-(3-(3-Bromo-5-chlorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-2-(trifluoromethyl)benzoicacid (C12)

Isolated as a brown gum (2.0 g, 62%): ¹H NMR (300 MHz, DMSO-d₆) δ 13.80(br s, 1H), 8.15 (s, 1H), 8.09 (d, J=8.1 Hz, 1H), 7.93-7.78 (m, 4H),6.91 (dd, J=35.7, 10.2 Hz, 1H), 5.27-5.14 (m, 1H); IR (thin film) 3081,2927, 1714, 776 cm⁻¹; ESIMS m/z 503 ([M−H]⁻).

(Z)-4-(3-(3,4-Dibromophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-2-(trifluoromethyl)benzoicacid (C13)

Isolated as a yellow gum (2.1 g, 78%): ¹H NMR (400 MHz, CDCl₃) δ 8.02(d, J=8.4 Hz, 1H), 7.94 (s, 1H), 7.83 (d, J=8.4 Hz, 1H), 7.66 (d, J=8.4Hz, 2H), 7.26-7.21 (m, 1H), 5.96 (dd, J=32.4, 9.2 Hz, 1H), 4.67-4.58 (p,1H); IR (thin film) 3426, 2925, 1714, 1115 cm⁻¹; ESIMS m/z 547 ([M−H]⁻).

(Z)-2-Methyl-4-(1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzoicacid (C14)

Isolated as an orange oil (0.94 g, 61%): ¹H NMR (400 MHz, CDCl₃) δ 8.09(d, J=8.8 Hz, 1H), 7.49-7.45 (m, 2H), 7.44 (s, 2H), 5.80 (dd, J=32.7,9.6 Hz, 1H), 4.60 (p, J=8.9 Hz, 1H), 2.69 (s, 3H); ¹⁹F NMR (376 MHz,CDCl₃) δ −69.40 (d, J=2.3 Hz), −108.40-−115.65 (m); ESIMS m/z 441([M−H]⁻).

(Z)-2-Methyl-4-(1,4,4-trifluoro-3-(3,4,5-trichlorophenyl)pent-1-en-1-yl)benzoicacid (C15)

Isolated as an orange foam (0.204 g, 51%): ¹H NMR (400 MHz, CDCl₃) δ8.07 (d, J=8.8 Hz, 1H), 7.49-7.40 (m, 4H), 5.86 (dd, J=33.9, 9.9 Hz,1H), 4.27 (td, J=14.3, 9.7 Hz, 1H), 2.68 (s, 3H), 1.65 (t, J=18.4 Hz,3H); ¹⁹F NMR (376 MHz, CDCl₃) δ −95.11, −95.18, −114.57; ESIMS m/z 437([M−H]⁻).

(Z)-4-(1,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)hex-1-en-1-yl)-2-(trifluoromethyl)benzoicacid (C16)

Isolated as an orange foam (0.136 g, 63%): ¹H NMR (400 MHz, CDCl₃) δ7.99 (dd, J=8.4, 4.0 Hz, 1H), 7.93 (s, 1H), 7.80 (d, J=7.9 Hz, 1H), 7.42(d, J=2.6 Hz, 2H), 6.08-5.87 (m, 1H), 4.32 (td, J=14.6, 9.8 Hz, 1H),1.87 (ddt, 1=21.6, 15.4, 8.0 Hz, 2H), 1.07 (t, J=7.4 Hz, 3H); ¹³C NMR(101 MHz, CDCl₃) δ 170.72, 156.96 (d, J_(CF)=253.0 Hz), 136.85, 135.06,134.53, 133.75, 131.90, 131.19, 130.18, 129.17, 128.60, 128.05, 127.29,124.11, 123.36-122.67 (m), 121.39, 104.66 (d, J_(CF)=18.0 Hz), 46.46,29.70-27.14 (m), 6.40-5.44 (m); ESIMS m/z 503 ([M−H]⁻).

(Z)-4-(3-(3,4-Dichlorophenyl)-1,4,4-trifluoropent-1-en-1-yl)-2-(trifluoromethyl)benzoicacid (C17)

Isolated as an orange glass (0.495 g, 51%): ¹H NMR (400 MHz, CDCl₃) δ8.01 (d, J=8.2 Hz, 1H), 7.94 (d, J=1.6 Hz, 1H), 7.80 (dd, J=8.2, 1.8 Hz,1H), 7.49 (d, J=2.1 Hz, 1H), 7.45 (d, J=8.3 Hz, 1H), 7.26 7.22 (m, 1H),6.00 (dd, J=33.9, 9.8 Hz, 1H), 4.32 (ddd, J=15.8, 13.0, 9.8 Hz, 1H),1.62 (t, J=18.4 Hz, 3H); ¹⁹F NMR (376 MHz, CDCl₃) δ −59.58,−89.79-−99.81 (m) −115.63; IR (thin film) 3008, 1711 cm⁻¹; ESIMS m/z 455([M−H]⁻).

(Z)-4-(3-(3,4-Dichlorophenyl)-1,4,4-trifluoropent-1-en-1-yl)-2-(trifluoromethyl)benzoicacid (C18)

Isolated as a brown gum (2.5 g, 46%): ¹H NMR (300 MHz, DMSO-d₆) δ 13.79(br s, 1H), 8.15-8.06 (m, 3H), 7.91 (d, J=8.1 Hz, 1H), 7.71 (s, 2H),6.90 (dd, J=36.0, 10.2 Hz, 1H), 5.21-5.15 (m, 1H); IR (thin film) 3431,2924, 1623, 597 cm⁻¹; ESIMS m/z 503 ([M−H]⁻).

(Z)-4-(3-(3-Chloro-4-fluorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-2-(trifluoromethyl)benzoicacid (C19)

Isolated as a yellow gum (1.50 g, 57%): ¹H NMR (300 MHz, CDCl₃) δ 8.01(d, J=8.1 Hz, 2H) 7.94 (s, 2H), 7.76-7.75 (m, 1H), 7.37 (d, J=6.0 Hz,2H), 5.90 (dd, J=32.1, 9.0 Hz, 1H); IR (thin film) 3445, 2926, 1698,1260, 750 cm⁻¹; ESIMS m/z 443 ([M−H]⁻).

(Z)-4-(3-(4-Chloro-3-fluorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-2-(trifluoromethyl)benzoicacid (C20)

Isolated as a brown gum (0.50 g, 48%): ¹H NMR (300 MHz, CDCl₃) δ 8.03(d, J=8.1 Hz, 1H), 7.94 (s, 1H), 7.83 (d, J=7.8 Hz, 1H), 7.46-7.44 (m,1H), 7.23-7.13 (m, 2H), 5.98 (dd, J=34.2, 9.9 Hz, 1H), 4.69-4.63 (m,1H); IR (thin film) 3092, 1751, 750 cm⁻¹; ESIMS m/z 443 ([M−H]⁻).

(Z)-4-(1,4,4,4-Tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzoicacid (CC1)

Isolated as a yellow gum (1.1 g, 56%): ¹H NMR (400 MHz, CDCl₃) δ 8.15(d, J=8.2 Hz, 2H), 7.67 (d, J=8.3 Hz, 2H), 7.44 (s, 2H), 5.84 (dd,J=32.6, 9.6 Hz, 1H), 4.61 (p, J=8.9 Hz, 1H); ¹⁹F NMR (376 MHz, CDCl₃) δ−69.38 (d, J=2.2 Hz), −109.75-−116.47 (m); ESIMS m/z 427 ([M−H]⁻).

Example 2: Preparation of(Z)-2-iodo-4-(1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzoicacid (C21)

To a 25 mL vial were added(Z)-2-bromo-4-(1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzoicacid (C1) (0.500 g, 0.987 mmol), copper(I) iodide (0.0094 g, 0.049mmol), and 1,4-dioxane (4.9 mL) to form a yellow suspension. Sodiumiodide (0.296 g, 1.97 mmol) andtrans-N,N′-dimethylcyclohexane-1,2-diamine (0.014 g, 0.099 mmol) wereadded, and the reaction mixture was stirred at 110° C. for 3.5 hours.The reaction mixture was concentrated and purified by flash columnchromatography to provide the title compound as a brown oil (0.247 g,43%): ¹H NMR (300 MHz, CDCl₃) δ 8.21 (d, J=1.7 Hz, 1H), 8.02 (d, J=8.2Hz, 1H), 7.62 (dd, J=8.3, 1.7 Hz, 1H), 7.43 (s, 2H), 5.82 (dd, J=32.5,9.6 Hz, 1H), 4.59 (p, J=8.9 Hz, 1H); ¹⁹F NMR (471 MHz, CDCl₃) δ −69.32,−112.14 (d, J=20.8 Hz); ESIMS m/z 553 ([M−H]⁻).

Example 3: Preparation of(Z)-2-iodo-4-(1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzoicacid (C22)

Tetrakis(triphenylphosphine)palladium(0) (0.30 g, 0.26 mmol) was addedto a solution of(Z)-4-(3-(4-bromo-3,5-dichlorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-2-(trifluoromethyl)benzoicacid (C11) (1.4 g, 2.6 mmol) in toluene (10 mL) at room temperature. Thereaction mixture was degassed by purging with nitrogen (3×10 minutes).Tributyl vinyl stannane (0.82 g, 2.6 mmol) was added to the reactionmixture. The reaction mixture was again degassed by purging withnitrogen (3×10 minutes) and stirred at 120° C. for 3 hours. The reactionmixture was quenched with water and then extracted with ethyl acetate.The organic layer was dried over sodium sulfate, filtered, andconcentrated. Purification by flash column chromatography using 30%ethyl acetate/hexanes provided the title compound as a pale yellow gum(0.80 g, 63%): ¹H NMR (300 MHz, CDCl₃) δ 7.85 (s, 1H), 7.82 (d, J=8.4Hz, 1H), 7.74 (d, J=8.4 Hz, 1H), 7.42 (s, 1H), 7.37 (s, 1H), 6.72-6.65(dd, J=17.6 Hz, 11.6 Hz, 1H), 5.86-5.73 (m, 3H), 4.61-4.56 (m, 1H); IR(thin film) 3445, 2925, 1646, 1275, 749 cm⁻¹; ESIMS m/z 488 ([M+H]⁺).

Example 4: Preparation of(Z)-4-(1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzoylchloride (C23)

To a 25 mL vial was added(Z)-4-(1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzoicacid (C2) (0.200 g, 0.404 mmol), oxalyl chloride (0.095 mL, 1.09 mmol),and N,N-dimethylformamide (catalytic amount) in dichloromethane (1.3 mL)to give a yellow solution. The reaction was stirred for 15 hours at roomtemperature. The solvent was removed under vacuum providing the titlecompound as a yellow gum (0.220 g, 95%): ¹H NMR (400 MHz, CDCl₃) δ 7.99(d, J=8.2 Hz, 1H), 7.92 (d, J=1.7 Hz, 1H), 7.81 (dd, J=8.2, 1.8 Hz, 1H),7.44 (s, 2H), 5.88 (dd, J=32.5, 9.6 Hz, 1H), 4.73-4.50 (m, 1H); ¹⁹F NMR(376 MHz, CDCl₃) δ −59.58, −69.32, −109.75-−113.19 (m); IR (thin film)3445, 2925, 1646, 1275, 749 cm⁻¹; ESIMS m/z 476 ([M−Cl]⁺).

Example 5: Preparation of 2-bromo-4-(1-fluorovinyl)benzoic acid (C24)

To a 250 mL round-bottomed flask were added methyl2-bromo-4-(1-fluorovinyl)benzoate (C29) (1.8 g, 7.0 mmol), lithiumhydroxide hydrate (0.88 g, 21 mmol), methanol (7.0 mL), tetrahydrofuran(21 mL), and water (7.0 mL), and the reaction mixture was stirredovernight at room temperature. The mixture was concentrated, quenchedwith a pH 4 buffer, and extracted with ethyl acetate to provide thetitle compound as a white solid (1.0 g, 56%): ¹H NMR (400 MHz, CDCl₃) δ8.01 (d, J=8.2 Hz, 1H), 7.89 (d, J=1.8 Hz, 1H), 7.57 (dd, J=8.3, 1.8 Hz,1H), 5.21 (dd, J=48.6, 4.0 Hz, 1H), 5.06 (dd, J=17.3, 3.9 Hz, 1H); ¹⁹FNMR (471 MHz, CDCl₃) δ −108.71 (d, J=1.4 Hz); ESIMS m/z 244 ([M−H]⁻).

The following compounds were prepared in like manner to the procedureoutlined in Example 5:

4-(1-Fluorovinyl)-2-(trifluoromethyl)benzoic acid (C25)

Isolated as a white solid (1.9 g, 93%): ¹H NMR (400 MHz, methanol-d₄) δ7.95 (d, J=1.5 Hz, 1H), 7.95-7.91 (m, 1H), 7.90-7.86 (m, 1H), 5.46 (dd,J=50.0, 4.1 Hz, 1H), 5.09 (dd, J=18.0, 4.1 Hz, 1H); ¹⁹F NMR (376 MHz,methanol-d₄) δ −61.04 (d, J=1.1 Hz), −110.93; ESIMS m/z 233 ([M−H]⁻).

2-Chloro-4-(1-fluorovinyl)benzoic acid (C26)

Isolated as a white solid (3.5 g, 75%): ¹H NMR (400 MHz, acetone-d₆) δ7.97 (dd, J=8.2, 0.9 Hz, 1H), 7.76 (d, J=1.7 Hz, 1H), 7.70 (dd, J=8.2,1.7 Hz, 1H), 5.68-5.45 (m, 1H), 5.11 (dd, J=18.2, 4.1 Hz, 1H); ¹⁹F NMR(376 MHz, acetone-d₆) δ −108.71; ESIMS m/z 200 ([M−H]⁻).

4-(1-fluorovinyl)-2-methylbenzoic acid (C27)

Isolated as a white solid (0.550 g, 89%): ¹H NMR (400 MHz, methanol-d₄)δ 7.92 (d, J=8.1 Hz, 1H), 7.59-7.52 (m, 1H), 7.52-7.44 (m, 1H), 5.29(dd, J=50.1, 3.7 Hz, 1H), 4.93 (dd, J=18.1, 3.7 Hz, 1H), 2.60 (s, 3H);¹⁹F NMR (376 MHz, methanol-d₄) δ −110.32 (d, J=2.1 Hz); ESIMS m/z 181([M+H]⁺).

Example 6: Preparation of methyl4-(1-fluorovinyl)-2-(trifluoromethyl)benzoate (C28)

To a 100 mL round-bottomed flask was added methyl4-bromo-2-(trifluoromethyl)benzoate (2.25 g, 8.00 mmol),(1-fluorovinyl)(methyl)diphenylsilane (3.58 g, 14.8 mmol), and1,3-dimethylimidazolidin-2-one (40 mL).Tetrakis(triphenylphosphine)palladium(0) (0.459 g, 0.400 mmol),copper(I) iodide (0.0760 mg, 0.400 mmol), and cesium fluoride (3.62 g,23.9 mmol) were added and the reaction was stirred at room temperaturefor 24 hours under a nitrogen atmosphere. Water was added to the mixtureand the mixture was diluted with 3:1 hexanes/diethyl ether. The layerwas separated, and the organic layer was dried over sodium sulfate,concentrated, and the residue was purified by flash columnchromatography provided the title compound as a colorless oil (2.00 g,96%): ¹H NMR (400 MHz, CDCl₃) δ 7.96-7.87 (m, 1H), 7.83 (dq, J=8.1, 0.7Hz, 1H), 7.77 (dd, J=8.2, 1.7 Hz, 1H), 5.23 (dd, J=48.6, 4.0 Hz, 1H),5.07 (dd, J=17.4, 4.0 Hz, 1H), 3.95 (s, 3H); ¹⁹F NMR (376 MHz, CDCl₃) δ−59.92, −108.73 (d, J=1.4 Hz); EIMS m/z 248 ([M]⁺).

The following compounds were prepared in like manner to the procedureoutlined in Example 6:

Methyl 2-bromo-4-(1-fluorovinyl)benzoate (C29)

Isolated as a colorless oil (1.8 g, 93%): ¹H NMR (400 MHz, CDCl₃) δ 7.84(d, J=1.7 Hz, 1H), 7.82 (dd, J=8.2, 0.9 Hz, 1H), 7.50 (d, J=1.5 Hz, 1H),5.16 (dd, J=48.7, 3.9 Hz, 1H), 5.01 (dd, J=17.3, 3.9 Hz, 1H), 3.94 (d,J=2.2 Hz, 3H); ¹⁹F NMR (376 MHz, CDCl₃) δ −108.61 (d, J=1.5 Hz); ESIMSm/z 258 ([M−H]⁻).

Methyl 2-chloro-4-(1-fluorovinyl)benzoate (C30)

Isolated as a colorless oil (2.1 g, 99%): ¹H NMR (400 MHz, CDCl₃) δ 7.86(dd, J=8.2, 0.9 Hz, 1H), 7.64 (d, J=1.7 Hz, 1H), 7.48 (dd, J=8.3, 1.8Hz, 1H), 5.17 (dd, J=48.7, 3.8 Hz, 1H), 5.02 (dd, J=17.3, 3.9 Hz, 1H),3.94 (s, 3H); ¹⁹F NMR (376 MHz, CDCl₃) δ −108.63 (d, J=1.4 Hz); ESIMSm/z 214 ([M−H]⁻).

Methyl 2-chloro-4-(1-fluorovinyl)benzoate (C31)

Isolated as a colorless oil (0.5 g, 85%): ¹H NMR (400 MHz, methanol-d₄)δ 7.90 (d, J=8.2 Hz, 1H), 7.51 (s, 1H), 7.49 (dd, J=8.0, 1.6 Hz, 1H),5.30 (dd, J=50.1, 3.7 Hz, 1H), 4.95 (dd, J=18.0, 3.7 Hz, 1H), 3.88 (d,J=5.9 Hz, 3H), 2.59 (s, 3H); ¹⁹F NMR (376 MHz, methanol-d₄) δ −110.41(d, J=1.3 Hz); ESIMS m/z 195 ([M+H]⁺).

Example 7: Preparation of 4-(1-fluorovinyl)-2-(trifluoromethyl)benzoicacid (C25)

Step 1: 4-(2-bromo-1-fluoroethyl)-2-(trifluoromethyl)benzoic acid (C32)

2-(Trifluoromethyl)-4-vinylbenzoic acid (5.3 g, 24 mmol) was dissolvedin dichloromethane (123 mL) at 0° C., triethylamine trihydrofluoride wasadded (8.0 mL, 49 mmol) followed by N-bromosuccinimide (8.7 g, 49 mmol).The reaction mixture was stirred for 16 hours while warming to roomtemperature. Water was then added to the mixture, washed withdichloromethane, dried over sodium sulfate, filtered, and concentratedproviding the title compound as a yellow oil which was used withoutfurther purification (5.0 g, 65%).

Step 2: 4-(1-fluorovinyl)-2-(trifluoromethyl)benzoic acid (C25)

4-(2-Bromo-1-fluoroethyl)-2-(trifluoromethyl)benzoic acid (4.3 g, 14mmol) was dissolved in methanol (68 mL) at 0° C. and potassiumtert-butoxide (4.6 g, 41 mmol) was added as a solid while stirring. Thereaction mixture was allowed to slowly warm to 23° C. and then stirredfor 4 hours. Hydrochloric acid (1 N) was slowly added, and the mixturewas extracted with ethyl acetate. Purification by flash columnchromatography using 0-40% acetone/hexanes provided the title compoundas an off-white solid (1.7 g, 53%): ¹H NMR (400 MHz, CDCl₃) δ 8.02 (d,J=8.2 Hz, 1H), 8.00-7.93 (m, 1H), 7.82 (dd, J=8.2, 1.8 Hz, 1H), 5.27(dd, J=48.5, 4.1 Hz, 1H), 5.11 (dd, J=17.3, 4.1 Hz, 1H).

The following compounds were prepared in like manner to the procedureoutlined in Example 7:

4-(1-Fluorovinyl)benzoic acid (C33)

Isolated as a white solid (6.5 g, 86%): ¹H NMR (400 MHz, CDCl₃) δ 8.13(d, J=8.2 Hz, 2H), 7.69-7.62 (m, 2H), 5.21 (dd, J=49.0, 3.7 Hz, 1H),5.02 (dd, J=17.5, 3.7 Hz, 1H); ¹⁹F NMR (376 MHz, CDCl₃) δ −108.35; ESIMSm/z 165 ([M−H]⁻).

4-(1-Fluorovinyl)-2-methylbenzoic acid (C27)

Isolated as a colorless oil (0.165 g, 89%): ¹H NMR (400 MHz, CDCl₃) δ8.12-8.03 (m, 1H), 7.46 (dd, J=5.8, 2.1 Hz, 2H), 5.17 (dd, J=49.1, 3.7Hz, 1H), 4.98 (dd, J=17.5, 3.7 Hz, 1H), 2.68 (s, 3H); ¹⁹F NMR (376 MHz,CDCl₃) 5-108.50.

Example 8: Preparation of5-(1-bromo-2,2-difluoropropyl)-1,2,3-trichlorobenzene (C34)

N-Bromosuccinimide (12.0 g, 67.5 mmol) was added to a solution of2,2-difluoro-1-(3,4,5-trichlorophenyl)propan-1-ol (C43) (6.00 g, 21.8mmol) in dichloromethane (72.6 mL). To this stirred solution was addedtriphenyl phosphite (17.1 mL, 65.3 mmol) slowly, dropwise, and thereaction mixture became dark brown. The reaction mixture was then heatedat reflux for 3 hours. The solvent was concentrated, and the residue wastriturated with diethyl ether. The solid was filtered, the filtrate wasconcentrated and the resultant oil was purified by flash columnchromatography using hexanes as eluent to provide the title compound asa clear and colorless oil (2.20 g, 25%): ¹H NMR (400 MHz, CDCl₃) δ 7.52(s, 2H), 4.85 (dd, J=12.3, 10.4 Hz, 1H), 1.77 (t, J=18.2 Hz, 3H); ¹⁹FNMR (376 MHz, CDCl₃) δ −92.14-−95.01 (m); EIMS m/z 338 ([M]⁺).

The following compounds were prepared in like manner to the procedureoutlined in Example 8:

1,3-Dibromo-5-(1-bromo-2,2,2-trifluoroethyl)-2-chlorobenzene (C35)

Isolated as a clear oil (28 g, 56%): ¹H NMR (400 MHz, DMSO-d₆) δ8.01-7.97 (m, 2H), 6.26-6.20 (m, 1H); IR (thin film) 1168, 736, 557cm⁻¹; ESIMS m/z 428 ([M+H]⁺).

5-(1-Bromo-2,2,2-trifluoroethyl)-2-chloro-1,3-dimethylbenzene (C36)

Isolated as a clear oil (6.32 g, 89%): ¹H NMR (300 MHz, DMSO-d₆) δ 7.39(s, 2H), 6.17-6.09 (m, 1H), 2.35 (s, 6H); IR (thin film) 1114, 754 cm⁻¹;ESIMS m/z 302 ([M+H]⁺).

2-Bromo-5-(1-bromo-2,2,2-trifluoroethyl)-1,3-dichlorobenzene (C37)

Isolated as a clear oil (19 g, 46%): ¹H NMR (400 MHz, CDCl₃) δ 7.54-7.51(m, 2H), 5.03-4.98 (m, 1H); ¹⁹F NMR (376 MHz, CDCl₃) δ 10-70.38.

4-(1-Bromo-2,2-difluoropropyl)-1,2-dichlorobenzene (C38)

Isolated as a colorless liquid (1.40 g, 65%): ¹H NMR (300 MHz, DMSO-d₆)δ 7.76-7.70 (m, 2H), 7.54 (dd, J=8.4, 1.8 Hz, 1H), 5.81-5.73 (m, 1H),1.67 (d, 1=18.9 Hz, 3H); IR (thin film) 1118, 800, 499 cm⁻¹; EIMS m/z304 ([M]⁺).

2-Bromo-4-(1-bromo-2,2,2-trifluoroethyl)-1-chlorobenzene (C39)

Isolated as a colorless liquid (10.5 g, 54%): ¹H NMR (400 MHz, CDCl₃) δ7.76 (d, J=1.2 Hz, 1H), 7.49-7.47 (m, 1H), 7.41-7.39 (m, 1H), 5.07-5.02(m, 1H); IR (thin film) 3437, 2924, 1631, 1114 cm⁻¹; EIMS m/z 350([M]⁺).

4-(1-Bromo-2,2,2-trifluoroethyl)-2-chloro-1-fluorobenzene (C40)

Isolated as a colorless oil (8.0 g, 73%): ¹H NMR (300 MHz, CDCl₃) δ7.59-7.57 (m, 1H), 7.42-7.33 (m, 1H), 7.20-7.14 (m, 1H), 5.10-5.03 (m,1H); IR (thin film) 3429, 2926, 1502, 750 cm⁻¹; ESIMS m/z 292 ([M+H]⁺).

4-(1-Bromo-2,2,2-trifluoroethyl)-1-chloro-2-fluorobenzene (C41)

Isolated as a yellow oil (1.1 g, 45%): ¹H NMR (400 MHz, CDCl₃) δ 7.44(dd, J=8.3, 7.5 Hz, 2H), 7.34 (dd, J=9.5, 1.9 Hz, 1H), 7.26-7.22 (m,1H), 5.08 (q, J=7.1 Hz, 1H); EIMS m/z 291 ([M]⁺).

Example 9: Preparation of5-(1-bromo-2,2-difluorobutyl)-1,2,3-trichlorobenzene (C42)

Triethylamine (2.46 mL, 17.6 mmol) and methanesulfonyl chloride (1.10mL, 14.1 mmol) were added to a solution of2,2-difluoro-1-(3,4,5-trichlorophenyl)butan-1-ol (C44) (3.40 g, 11.7mmol) in dichloromethane (58.7 mL). The reaction mixture was stirred for1 hour, and then pentane was added. Filtration followed by concentrationof the filtrate under vacuum provided a white solid. The solid wasdissolved in dichloromethane (58.7 mL) to which iron(III) bromide (6.94g, 23.5 mmol) was added. The reaction mixture was stirred overnight. Themixture was poured into water and then extracted with dichloromethane.The organics were washed with brine, dried over sodium sulfate,filtered, and concentrated. Purification by flash column chromatographyusing hexanes as eluent provided the title compound as a white solid(3.52 g, 72%): ¹H NMR (400 MHz, CDCl₃) δ 7.51 (s, 2H), 4.85 (t, J=12.1Hz, 1H), 2.14-1.91 (m, 2H), 1.06 (t, J=7.5 Hz, 3H); ¹³C NMR (101 MHz,CDCl₃) δ 135.55, 134.39, 132.52, 129.48, 120.25 (t, J=249.0 Hz), 49.76(t, J=30.3 Hz), 28.03 (t, J=25.2 Hz), 6.06 (t, J=5.1 Hz); ESIMS m/z 351([M−H]⁻).

Example 10: Preparation of2,2-difluoro-1-(3,4,5-trichlorophenyl)propan-1-ol (C43)

2,2-Difluoro-1-(3,4,5-trichlorophenyl)propan-1-one (C52) (1.75 g, 6.40mmol) was dissolved in methanol (64.0 mL) at room temperature and sodiumborohydride (0.290 g, 7.68 mmol) was added. The reaction stirred at roomtemperature for 1 hour, until gas evolution ceased. The reaction mixturewas poured into water and extracted with diethyl ether. The organiclayer was washed with brine, dried over sodium sulfate, filtered, andconcentrated. Purification by flash column chromatography using 0-30%acetone/hexanes as eluent provided the title compound as a clear,colorless oil (1.60 g, 91%): ¹H NMR (400 MHz, CDCl₃) δ 7.50 (d, J=0.9Hz, 2H), 4.81 (td, J=8.7, 3.8 Hz, 1H), 1.65-1.41 (m, 3H); ¹⁹F NMR (376MHz, CDCl₃) δ −98.54-−101.73 (m); IR (thin film) 3405, 1555, 1389 cm⁻¹.

The following compounds were prepared in like manner to the procedureoutlined in Example 10:

2,2-Difluoro-1-(3,4,5-trichlorophenyl)butan-1-ol (C44)

Isolated as a clear and colorless oil (3.4 g, 48%): ¹H NMR (400 MHz,CDCl₃) δ 7.48 (d, J=0.9 Hz, 2H), 4.87-4.70 (m, 1H), 2.54 (dt, J=4.0, 1.0Hz, 1H), 2.06-1.82 (m, 1H), 1.82-1.63 (m, 1H), 1.02 (t, J=7.5 Hz, 3H);¹³C NMR (101 MHz, CDCl₃) δ 136.85, 134.20, 131.60, 127.54, 123.19 (t,J=248.0 Hz), 73.71 (t, J=30.0 Hz), 25.05 (t, J=24.6 Hz), 5.35 (t, J=5.2Hz); EIMS m/z 287 ([M]⁺).

1-(3,4-Dichlorophenyl)-2,2-difluoropropan-1-ol (C45)

Isolated as a clear and colorless oil (2.78 g, 89%): ¹H NMR (400 MHz,CDCl₃) δ 7.57 (dd, J=2.0, 0.9 Hz, 1H), 7.46 (d, J=8.3 Hz, 1H), 7.33-7.27(m, 1H), 4.83 (td, J=8.9, 3.7 Hz, 1H), 2.55 (dt, =3.8, 1.1 Hz, 1H), 1.50(t, J=18.9 Hz, 3H); ¹⁹F NMR (376 MHz, CDCl₃) δ −99.52 (d, J=249.6 Hz),−101.09 (d, J=249.4 Hz); IR (thin film) 3417 cm⁻¹.

Example 11: Preparation of1-(3-bromo-4-chlorophenyl)-2,2,2-trifluoroethanol (C46)

Trimethyl(trifluoromethyl)silane (10.1 mL, 68.4 mmol) andtetrabutylammonium fluoride (1.44 g, 4.56 mmol) were added to a stirredsolution of 3-bromo-4-chloro-benzaldehyde (10.0 g, 45.6 mmol) intetrahydrofuran (150 mL) at room temperature and the reaction mixturewas stirred for 2 hours. The reaction mixture was diluted withdichloromethane and washed with hydrochloric acid (2 N). The separatedorganic layer was washed with brine, dried over sodium sulfate,filtered, and concentrated to afford the title compound as a brownliquid that was used without further purification (13.2 g, 94%): ¹H NMR(300 MHz, CDCl₃) δ 7.76 (s, 1H), 7.50-7.48 (m, 1H), 7.38-7.35 (m, 1H),5.03-4.97 (m, 1H), 2.95 (br s, 1H); IR (thin film) 3406, 2881, 1469, 814cm⁻¹; EIMS m/z 288 ([M]⁺).

The following compounds were prepared in like manner to the procedureoutlined in Example 11:

1-(3,5-Dibromo-4-chlorophenyl)-2,2,2-trifluoroethanol (C47)

Isolated as a pale yellow liquid (7.4 g, 85%): ¹H NMR (400 MHz, DMSO-d₆)δ 7.90 (s, 2H), 7.24 (d, J=5.2 Hz, 1H), 5.33 (d, J=6.4 Hz, 1H); IR (thinfilm) 3370, 1175, 735, 541 cm⁻¹; EIMS m/z 366 ([M]⁺).

1-(4-Chloro-3,5-dimethylphenyl)-2,2,2-trifluoroethanol (C48)

Isolated as a clear liquid (5.0 g, 70%): ¹H NMR (400 MHz, CDCl₃) δ 7.18(s, 2H), 4.95-4.92 (m, 1H), 2.40 (s, 6H); IR (thin film) 3378, 1124, 833cm⁻¹; EIMS m/z 238 ([M]⁺).

1-(4-Bromo-3,5-dichlorophenyl)-2,2,2-trifluoroethanol (C49)

Isolated as a clear oil (33 g, 86%): ¹H NMR (400 MHz, CDCl₃) δ 7.51 (s,2H), 5.01-4.96 (m, 1H), 4.14-4.09 (m, 1H); ¹⁹F NMR (376 MHz, CDCl₃) δ−78.32.

1-(3-Chloro-4-fluorophenyl)-2,2,2-trifluoroethanol (C50)

Isolated as a clear and brown gum (7.0 g, 97%): ¹H NMR (300 MHz, CDCl₃)δ 7.58-7.55 (m, 1H), 7.38-7.33 (m, 1H), 7.20-7.15 (m, 1H), 5.03-4.97 (m,1H); EIMS m/z 228 ([M]⁺).

1-(4-Chloro-3-fluorophenyl)-2,2,2-trifluoroethanol (C51)

Isolated as a clear and colorless oil (1.97 g, 75%): ¹H NMR (400 MHz,CDCl₃) δ 7.52-7.37 (m, 1H), 7.32 (d, J=9.6 Hz, 1H), 7.21 (d, J=8.3 Hz,1H), 5.03 (dd, J=6.3, 3.6 Hz, 1H), 2.62 (d, J=4.0 Hz, 1H); ¹³C NMR (101MHz, CDCl₃) δ 158.06 (J_(CF)=250.4), 134.40 (d, J_(CF)=6.6 Hz), 130.79,123.83 (d, J_(CF)=3.5 Hz), 122.4 (q, J_(CF)=188.9 Hz), 115.8 (d, J=25.3Hz), 71.65 (q, J_(CF)=31.6 Hz); EIMS m/z 228 ([M]⁺).

Example 12: Preparation of 2,2-difluoro-1-(3,4,5-trichlorophenyl)propan-1-one (C52)

To 5-bromo-1,2,3-trichlorobenzene (2.28 g, 8.76 mmol) dissolved indiethyl ether (39.8 mL) at −78° C. under nitrogen was addedn-butyllithium (3.50 mL, 8.76 mmol). The solution was stirred for 30minutes. To this was added ethyl 2,2-difluoropropanoate (1.10 g, 7.96mmol, as a 20% w/w solution in toluene) dropwise over 10 minutes, andthe reaction mixture was stirred for an additional hour. Saturatedaqueous ammonium chloride solution was added to the mixture and stirringwas continued as the reaction flask warmed to room temperature. Thereaction mixture was then extracted with diethyl ether, washed withwater and brine, dried over sodium sulfate, filtered, and concentrated.Purification by flash column chromatography provided the title compoundas a pale yellow oil (1.76 g, 73%): ¹H NMR (400 MHz, CDCl₃) δ 8.11 (d,J=0.9 Hz, 2H), 1.89 (t, 1=19.6 Hz, 3H); ¹⁹F NMR (376 MHz, CDCl₃) δ−92.66; ESIMS m/z 271 ([M−H]⁻).

The following compounds were prepared in like manner to the procedureoutlined in Example 12:

2,2-Difluoro-1-(3,4,5-trichlorophenyl)butan-1-one (C53)

Isolated as an oil (2.3 g, 68%) and used without further purification orcharacterization.

1-(3,4-Dichlorophenyl)-2,2-difluoropropan-1-one (C54)

Isolated as a colorless oil (3.89 g, 71%): ¹H NMR (400 MHz, CDCl₃) δ8.21-8.18 (m, 1H), 7.99-7.93 (m, 1H), 7.59 (dd, J=8.4, 4.2 Hz, 1H), 1.89(t, J=19.6 Hz, 3H); ¹⁹F NMR (376 MHz, CDCl₃) δ −92.08-−93.21 (m); EIMSm/z 238/240 ([M]⁺).

Example 13: Preparation of(Z)—N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)-4-(1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide(F1)

To a 25 mL vial was added(Z)-4-(1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzoicacid (C2) (0.105 g, 0.210 mmol) and dichloromethane (4 mL) to give ayellow solution. 2-Amino-N-(2,2,2-trifluoroethyl)acetamide hydrochloride(0.0610 g, 0.320 mmol) andbenzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate(0.165 g, 0.320 mmol) were then added. Triethylamine (0.120 mL, 0.850mmol) was added and the reaction mixture was stirred at room temperatureovernight. The reaction mixture was then concentrated and purified byflash column chromatography providing the title compound as a yellow gum(0.105 g, 74%).

The following compounds were prepared according to the proceduresdisclosed in Example 13:

N—((R)-1-Oxo-1-((2,2,2-trifluoroethyl)amino)propan-2-yl)-4-((Z)-1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide(F2)

Isolated as a yellow gum (0.120 g, 83%).

(Z)-4-(1,4,4,4-Tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-N-(1-((2,2,2-trifluoroethyl)carbamoyl)cyclopropyl)-2-(trifluoromethyl)benzamide(F3)

Isolated as a colorless oil (0.022 g, 48%).

(Z)-2-Methyl-N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)-4-(1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzamide(F6)

Isolated as an off-white gum (0.090 g, 86%).

2-Methyl-N—((R)-1-oxo-1-((2,2,2-trifluoroethyl)amino)propan-2-yl)-4-((Z)-1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzamide(F7)

Isolated as an off-white gum (0.088 g, 78%).

N—((R)-1-(Allylamino)-1-oxopropan-2-yl)-4-((Z)-1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide(F11)

Isolated as a yellow gum (0.069 g, 76%).

N—((R)-1-((2-Cyclopropylethyl)amino)-1-oxopropan-2-yl)-4-((Z)-1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide(F12)

Isolated as a yellow gum (0.09 g 77%).

N—((R)-1-(Methyl(2,2,2-trifluoroethyl)amino)-1-oxopropan-2-yl)-4-((Z)-1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide(F13)

Isolated as a yellow gum (0.032 g, 46%).

N—((R)-1-(Allylamino)-1-oxopropan-2-yl)-2-methyl-4-((Z)-1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzamide(F14)

Isolated as a yellow gum (0.031 g, 52%).

N—((R)-1-((2-Cyclopropylethyl)amino)-1-oxopropan-2-yl)-2-methyl-4-((Z)-1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzamide(F15)

Isolated as a yellow gum (0.026 g, 42%).

N—((R)-1-(Butylamino)-1-oxopropan-2-yl)-4-((Z)-1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide(F16)

Isolated as a colorless oil (0.032 g, 39%).

2-Bromo-N—((R)-1-oxo-1-((2,2,2-trifluoroethyl)amino)propan-2-yl)-4-((Z)-1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzamide(F18)

Isolated as a colorless oil (0.065 g, 77%).

(Z)-2-Bromo-N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)-4-(1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzamide(F19)

Isolated as a colorless oil (0.051 g, 62%).

N—((R)-1-(Ethyl(2,2,2-trifluoroethyl)amino)-1-oxopropan-2-yl)-4-((Z)-1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide(F20)

Isolated as a colorless oil (0.025 g, 55%).

(Z)-2-Chloro-N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)-4-(1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzamide (F22)

Isolated as a colorless oil (0.116 g, 85%).

2-Chloro-N—((R)-1-oxo-1-((2,2,2-trifluoroethyl)amino)propan-2-yl)-4-((Z)-1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzamide(F23)

Isolated as a colorless oil (0.090 g, 64%).

2-Bromo-N—((R)-1-(ethyl(2,2,2-trifluoroethyl)amino)-1-oxopropan-2-yl)-4-((Z)-1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzamide (F25)

Isolated as a yellow oil (0.096 g, 84%).

2-Methyl-N—((R)-1-oxo-1-((2,2,2-trifluoroethyl)amino)propan-2-yl)-4-((Z)-1,4,4-trifluoro-3-(3,4,5-trichlorophenyl)pent-1-en-1-yl)benzamide(F26)

Isolated as a yellow foam (0.035 g, 66%).

N—((R)-1-Oxo-1-((2,2,2-trifluoroethyl)amino)propan-2-yl)-4-((Z)-1,4,4-trifluoro-3-(3,4,5-trichlorophenyl)pent-1-en-1-yl)-2-(trifluoromethyl)benzamide(F29)

Isolated as a white foam (0.058 g, 80%).

N—((R)-1-((2,2-Difluoroethyl)amino)-1-oxopropan-2-yl)-4-((Z)-1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide(F30)

Isolated as a yellow oil (0.132 g, 89%).

2-Bromo-N—((R)-1-((2,2-difluoroethyl)amino)-1-oxopropan-2-yl)-4-((Z)-1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzamide(F31)

Isolated as a yellow oil (0.079 g, 74%).

2-Chloro-N—((R)-1-((2,2-difluoroethyl)amino)-1-oxopropan-2-yl)-4-((Z)-1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzamide(F32)

Isolated as a white solid (0.103 g, 76%).

4-((Z)-3-(3,5-Dibromophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N—((R)-1-oxo-1-((2,2,2-trifluoroethyl)amino)propan-2-yl)-2-(trifluoromethyl)benzamide(F33)

Isolated as a pale yellow solid (0.140 g, 57%).

(Z)-4-(3-(3,5-Dibromophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)-2-(trifluoromethyl)benzamide(F35)

Isolated as a pale yellow solid (0.145 g, 62%).

4-((Z)-3-(3,5-Dichloro-4-fluorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N—((R)-1-oxo-1-((2,2,2-trifluoroethyl)amino)propan-2-yl)-2-(trifluoromethyl)benzamide(F36)

Isolated as a pale yellow solid (0.170 g, 61%).

(Z)-4-(3-(3,5-Dichloro-4-fluorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)-2-(trifluoromethyl)benzamide(F38)

Isolated as a pale yellow solid (0.105 g, 52%).

(Z)-4-(3-(3,5-Dichlorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N-(1-((2,2,2-trifluoroethyl)carbamoyl)cyclopropyl)-2-(trifluoromethyl)benzamide(F39)

Isolated as a brown gum (0.110 g, 38%).

(Z)-4-(3-(3,5-Dichlorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)-2-(trifluoromethyl)benzamide(F40)

Isolated as a brown gum (0.120 g, 40%).

(Z)-4-(3-(3,4-Dichlorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N-(1-((2,2,2-trifluoroethyl)carbamoyl)cyclopropyl)-2-(trifluoromethyl)benzamide(F41)

Isolated as a pale yellow solid (0.110 g, 32%).

4-((Z)-3-(3,4-Dichlorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N—((R)-1-oxo-1-((2,2,2-trifluoroethyl)amino)propan-2-yl)-2-(trifluoromethyl)benzamide(F42)

Isolated as a brown solid (0.180 g, 65%).

(Z)-4-(3-(3,4-Dichlorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)-2-(trifluoromethyl)benzamide(F43)

Isolated as a brown solid (0.130 g, 40%).

(Z)-2-Chloro-N-(2-(methyl(2,2,2-trifluoroethyl)amino)-2-oxoethyl)-4-(1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzamide(F47)

Isolated as a colorless gum (0.099 g, 83%).

(Z)-2-Bromo-N-(2-(methyl(2,2,2-trifluoroethyl)amino)-2-oxoethyl)-4-(1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzamide(F48)

Isolated as a colorless gum (0.094 g, 81%).

2-Chloro-N—((R)-1-(methyl(2,2,2-trifluoroethyl)amino)-1-oxopropan-2-yl)-4-((Z)-1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzamide(F49)

Isolated as a colorless gum (0.107 g, 88%).

2-Bromo-N—((R)-1-(methyl(2,2,2-trifluoroethyl)amino)-1-oxopropan-2-yl)-4-((Z)-1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzamide(F50)

Isolated as a colorless gum (0.082 g, 69%).

(Z)—N-(2-(Methyl(2,2,2-trifluoroethyl)amino)-2-oxoethyl)-4-(1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide(F51)

Isolated as a yellow gum (0.107 g, 92%).

N—((R)-2-Ethyl-3-oxoisoxazolidin-4-yl)-4-((Z)-1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide(F53)

Isolated as a brown gum (0.100 g, 41%).

(Z)-4-(1,4,4,4-Tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-N-(1-(4,4,4-trifluorobutanoyl)cyclopropyl)-2-(trifluoromethyl)benzamide(F56)

Isolated as a yellow oil (0.092 g, 66%).

(Z)-4-(1,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)pent-1-en-1-yl)-N-(1-((2,2,2-trifluoroethyl)carbamoyl)cyclopropyl)-2-(trifluoromethyl)benzamide(F58)

Isolated as a white gum (0.070 g, 85%).

(Z)—N-(2-Oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)-4-(1,4,4-trifluoro-3-(3,4,5-trichlorophenyl)pent-1-en-1-yl)-2-(trifluoromethyl)benzamide(F62)

Isolated as a white foam (0.049 g, 64%).

N—((R)-1-(Ethylamino)-1-oxopropan-2-yl)-4-((Z)-1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide(F63)

Isolated as a yellow oil (0.089 g, 88%).

2-Chloro-N—((R)-1-(ethylamino)-1-oxopropan-2-yl)-4-((Z)-1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzamide(F64)

Isolated as a white gum (0.035 g, 45%).

(Z)—N-(2-Oxo-2-((1,1,1-trifluoropropan-2-yl)amino)ethyl)-4-(1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide(F65)

Isolated as a yellow gum (0.108 g, 98%).

(Z)-2-Chloro-N-(2-oxo-2-((1,1,1-trifluoropropan-2-yl)amino)ethyl)-4-(1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzamide(F66)

Isolated as a colorless gum (0.048 g, 98%).

2-Iodo-N—((R)-1-oxo-1-((2,2,2-trifluoroethyl)amino)propan-2-yl)-4-((Z)-1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzamide(F67)

Isolated as a brown oil (0.162 g, 64%).

4-((Z)-3-(3,4-Dibromophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N—((R)-1-oxo-1-((2,2,2-trifluoroethyl)amino)propan-2-yl)-2-(trifluoromethyl)benzamide(F79)

Isolated as a pale yellow solid (0.140 g, 55%).

4-((Z)-3-(3,5-Dichloro-4-fluorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N—((R)-1-(methyl(2,2,2-trifluoroethyl)amino)-1-oxopropan-2-yl)-2-(trifluoromethyl)benzamide(F81)

Isolated as a yellow gum (0.152 g, 60%).

(Z)-4-(3-(3,5-Dichloro-4-fluorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N-(2-(methyl(2,2,2-trifluoroethyl)amino)-2-oxoethyl)-2-(trifluoromethyl)benzamide(F82)

Isolated as a yellow gum (0.182 g, 64%).

4-((Z)-3-(3,5-Dibromophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N—((R)-1-(methyl(2,2,2-trifluoroethyl)amino)-1-oxopropan-2-yl)-2-(trifluoromethyl)benzamide(F83)

Isolated as a yellow gum (0.155 g, 56%).

(Z)-4-(3-(3,5-Dibromophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N-(2-(methyl(2,2,2-trifluoroethyl)amino)-2-oxoethyl)-2-(trifluoromethyl)benzamide(F84)

Isolated as a yellow gum (0.180 g, 67%).

(Z)—N-(2-Oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)-4-(1,4,4-trifluoro-3-(3,4,5-trichlorophenyl)hex-1-en-1-yl)-2-(trifluoromethyl)benzamide(F87)

Isolated as a white gum (0.052 g, 68%).

(Z)-4-(1,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)hex-1-en-1-yl)-N-(1-((2,2,2-trifluoroethyl)carbamoyl)cyclopropyl)-2-(trifluoromethyl)benzamide(F88)

Isolated as a white foam (0.048 g, 60%).

(Z)—N-(1-(Methyl(2,2,2-trifluoroethyl)carbamoyl)cyclopropyl)-4-(1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide(F96)

Isolated as a yellow gum (0.073 g, 64%).

(Z)-2-Chloro-N-(1-(methyl(2,2,2-trifluoroethyl)carbamoyl)cyclopropyl)-4-(1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzamide(F97)

Isolated as a yellow oil (0.021 g, 18%).

N—((R)-1-Oxo-1-((2,2,2-trifluoroethyl)amino)butan-2-yl)-4-((Z)-1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide(F98)

Isolated as a yellow gum (0.145 g, 98%).

2-Chloro-N—((R)-1-oxo-1-((2,2,2-trifluoroethyl)amino)butan-2-yl)-4-((Z)-1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzamide(F100)

Isolated as a colorless gum (0.035 g, 40%).

N—((R)-3-Oxo-2-(2,2,2-trifluoroethyl)isoxazolidin-4-yl)-4-((Z)-1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide(F106)

Isolated as a yellow gum (0.100 g, 31%).

(Z)-4-(3-(3,4-Dibromophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)-2-(trifluoromethyl)benzamide(F107)

Isolated as a pale yellow solid (0.126 g, 48%).

4-((Z)-3-(3,4-Dichlorophenyl)-1,4,4-trifluoropent-1-en-1-yl)-N—((R)-1-oxo-1-((2,2,2-trifluoroethyl)amino)propan-2-yl)-2-(trifluoromethyl)benzamide(F112)

Isolated as a white foam (0.052 g, 58%).

2-Bromo-4-((Z)-3-(3,4-dichlorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N—((R)-1-oxo-1-((2,2,2-trifluoroethyl)amino)propan-2-yl)benzamide(F123)

Isolated as a yellow gum (0.073 g, 63%).

(Z)-2-Bromo-4-(3-(3,4-dichlorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)benzamide (F124)

Isolated as a yellow gum (0.065 g, 60%).

(Z)-2-Bromo-4-(3-(3,4-dichlorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N-(1-((2,2,2-trifluoroethyl)carbamoyl)cyclopropyl)benzamide(F125)

Isolated as a yellow gum (0.094 g, 77%).

(Z)-4-(3-(3,4-Dichlorophenyl)-1,4,4-trifluoropent-1-en-1-yl)-N-(1-((2,2,2-trifluoroethyl)carbamoyl)cyclopropyl)-2-(trifluoromethyl)benzamide(F128)

Isolated as a white gum (0.045 g, 55%).

(Z)-4-(3-(3,4-Dichlorophenyl)-1,4,4-trifluoropent-1-en-1-yl)-N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)-2-(trifluoromethyl)benzamide(F129)

Isolated as a white gum (0.070 g, 90%).

4-((Z)-3-(3-Chloro-4-fluorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N—((R)-1-oxo-1-((2,2,2-trifluoroethyl)amino)propan-2-yl)-2-(trifluoromethyl)benzamide(F132)

Isolated as a yellow gum (0.121 g, 43%).

(Z)—N-(2-Oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)-4-(1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzamide(FC1)

Isolated as a white glass (0.043 g, 54%).

N—((R)-1-Oxo-1-((2,2,2-trifluoroethyl)amino)propan-2-yl)-4-((Z)-1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzamide(FC2)

Isolated as a white foam (0.067 g, 82%).

Example 14: Preparation of(Z)—N-(1-((2-cyclopropylethyl)carbamoyl)cyclopropyl)-4-(1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide(F4)

To a 25 mL round-bottomed flask was added(Z)-5-(4-(1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)phenyl)-6-oxa-4-azaspiro[2.4]hept-4-en-7-one(C56) (0.040 g, 0.071 mmol) and 2-cyclopropylethanamine (0.010 g, 0.11mmol) in dichloromethane (1 mL) to give a colorless solution. Thereaction mixture was stirred at room temperature overnight. The reactionmixture was concentrated. Purification by flash column chromatographyprovided the title compound as a colorless oil (0.046 g, 95%).

The following compounds were prepared according to the proceduresdisclosed in Example 14:

(Z)—N-(1-(Allylcarbamoyl)cyclopropyl)-4-(1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide(F5)

Isolated as a colorless oil (0.045 g, 97%).

(Z)—N-(1-(Allylcarbamoyl)cyclopropyl)-2-methyl-4-(1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzamide(F9)

Isolated as a colorless oil (0.033 g, 36%).

(Z)—N-(1-((2-Cyclopropylethyl)carbamoyl)cyclopropyl)-2-methyl-4-(1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzamide(F10)

Isolated as a colorless oil (0.028 g, 92%).

(Z)-4-(1,4,4,4-Tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-N-(1-((4,4,4-trifluorobutyl)carbamoyl)cyclopropyl)-2-(trifluoromethyl)benzamide(F89)

Isolated as a colorless oil (0.055 g, 99%).

(Z)-4-(1,4,4,4-Tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)-N-(1-((3,3,3-trifluoropropyl)carbamoyl)cyclopropyl)benzamide(F90)

Isolated as a colorless oil (0.052 g, 99%).

(Z)—N-(1-(Isopentylcarbamoyl)cyclopropyl)-4-(1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide(F91)

Isolated as a colorless gum (0.039 g, 80%).

(Z)—N-(1-((2,2-Difluoropropyl)carbamoyl)cyclopropyl)-4-(1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide(F92)

Isolated as a colorless gum (0.051 g, 99%).

(Z)—N-(1-((Cyclobutylmethyl)carbamoyl)cyclopropyl)-4-(1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide(F93)

Isolated as a colorless gum (0.051 g, 99%).

(Z)—N-(1-(Prop-2-yn-1-ylcarbamoyl)cyclopropyl)-4-(1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide(F94)

Isolated as a colorless gum (0.039 g, 84%).

(Z)—N-(1-((2,2-Difluoroethyl)carbamoyl)cyclopropyl)-4-(1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide(F95)

Isolated as a colorless oil (0.035 g, 73%).

(Z)—N-(1-((3,3-Difluorocyclobutyl)carbamoyl)cyclopropyl)-4-(1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide(F101)

Isolated as a white gum (0.015 g, 30%).

Example 15: Preparation of(Z)-4-(1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-N-(1-((2,2,2-trifluoroethyl)carbamoyl)cyclopropyl)-2-(trifluoromethyl)benzamide(F3)

To a 20 mL vial was added1-amino-N-(2,2,2-trifluoroethyl)cyclopropanecarboxamide hydrochloride(0.255 g, 1.17 mmol),(Z)-4-(1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzoylchloride (C24) (0.150 g, 0.290 mmol), and 1,2-dichloroethane (3 mL) togive a brown suspension. 4-Methylmorpholine (0.239 g, 2.33 mmol) wasadded and the reaction mixture was agitated twice by vortex and stirredat room temperature in a closed vessel overnight. The mixture wasdiluted with ethyl acetate and washed with citric acid (5%). The organicphase was concentrated. Purification by flash column chromatographyusing 0-30% ethyl acetate/hexanes as eluent provided the title compoundas a colorless oil (0.101 g, 50%).

The following compounds were prepared according to the proceduresdisclosed in Example 15:

(Z)-2-Methyl-4-(1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-N-(1-((2,2,2-trifluoroethyl)carbamoyl)cyclopropyl)benzamide(F8)

Isolated as an off-white gum (0.215 g, 68%).

(Z)-2-Bromo-4-(1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-N-(1-((2,2,2-trifluoroethyl)carbamoyl)cyclopropyl)benzamide(F21)

Isolated as a colorless oil (0.047 g, 39%).

N—((R)-1-(Methoxy(2,2,2-trifluoroethyl)amino)-1-oxopropan-2-yl)-4-((Z)-1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide(F24)

Isolated as a brown foam (0.118 g, 86%).

N—((R)-1-((Allyloxy)(2,2,2-trifluoroethyl)amino)-1-oxopropan-2-yl)-4-((Z)-1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide(F27)

Isolated as a brown foam (0.118 g, 83%).

(Z)-2-Chloro-4-(1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-N-(1-((2,2,2-trifluoroethyl)carbamoyl)cyclopropyl)benzamide(F28)

Isolated as a yellow oil (0.116 g, 82%).

(Z)—N-(2-Methyl-1-oxo-1-((2,2,2-trifluoroethyl)amino)propan-2-yl)-4-(1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide(F54)

Isolated as a yellow oil (0.050 g, 37%).

tert-Butyl2-((2R)-2-(4-((Z)-1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamido)propanoyl)-2-(2,2,2-trifluoroethyl)hydrazinecarboxylate (F55)

Isolated as a brown foam (0.180 g, 97%).

(Z)—N-Methyl-N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)-4-(1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide(F68)

Isolated as a brown/glass foam (0.180 g, 64%).

(Z)—N-Methyl-N-(2-(methyl(2,2,2-trifluoroethyl)amino)-2-oxoethyl)-4-(1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide(F99)

Isolated as a brown/glass foam (0.163 g, 57%).

(Z)—N-(2-Oxo-1-(2,2,2-trifluoroethyl)piperidin-3-yl)-4-(1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide(F104)

Isolated as a beige foam (0.066 g, 57%).

N—((R)-1-Amino-1-oxobutan-2-yl)-4-((Z)-1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide(F126)

Isolated as an orange solid (0.820 g, 60%).

(Z)—N-(2-Amino-2-oxoethyl)-4-(1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide(F127)

Isolated as an orange solid (0.850 g, 65%).

Example 16: Preparation of(Z)-4-(3-(3,5-dibromophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N-(1-((2,2,2-trifluoroethyl)carbamoyl)cyclopropyl)-2-(trifluoromethyl)benzamide(F34)

Diisopropylethylamine (0.17 mL, 0.98 mmol),2-chloro-1,3-dimethylimidazolidinium hexafluorophosphate (0.091 g, 0.32mmol), 1-hydroxy-7-azabenzotriazole (0.044 g, 0.32 mmol), and1-amino-N-(2,2,2-trifluoroethyl)cyclopropanecarboxamide (0.086 g, 0.39mmol) were added to a solution of(Z)-4-(3-(3,5-dibromophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-2-(trifluoromethyl)benzoicacid (0.18 g, 0.33 mmol) in dichloromethane at room temperature, and themixture was stirred for 6 hours. The reaction mixture was diluted withdichloromethane and washed with water. The separated organic layer wasdried over sodium sulfate, filtered, and concentrated. Purification byflash column chromatography using 25% ethyl acetate/petroleum ether aseluent provided the title compound as a pale yellow solid (0.13 g, 48%).

The following compounds were prepared according to the proceduresdisclosed in Example 16:

(Z)-4-(3-(3,5-Dichloro-4-fluorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N-(1-((2,2,2-trifluoroethyl)carbamoyl)cyclopropyl)-2-(trifluoromethyl)benzamide(F37)

Isolated as a pale yellow solid (0.155 g, 55%).

4-((Z)-3-(3,5-Dibromo-4-chlorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N—((R)-1-oxo-1-((2,2,2-trifluoroethyl)amino)propan-2-yl)-2-(trifluoromethyl)benzamide(F44)

Isolated as a pale yellow solid (0.125 g, 27%).

(Z)-4-(3-(3,5-Dibromo-4-chlorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N-(1-((2,2,2-trifluoroethyl)carbamoyl)cyclopropyl)-2-(trifluoromethyl)benzamide(F45)

Isolated as a yellow solid (0.107 g, 25%).

(Z)-4-(3-(3,5-Dibromo-4-chlorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)-2-(trifluoromethyl)benzamide(F46)

Isolated as a yellow solid (0.105 g, 29%).

4-((Z)-3-(3,5-Dichloro-4-vinylphenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N—((R)-1-oxo-1-((2,2,2-trifluoroethyl)amino)propan-2-yl)-2-(trifluoromethyl)benzamide(F52)

Isolated as a pale yellow gum (0.080 g, 34%).

4-((Z)-3-(4-Bromo-3,5-dichlorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N—((R)-1-oxo-1-((2,2,2-trifluoroethyl)amino)propan-2-yl)-2-(trifluoromethyl)benzamide(F59)

Isolated as a yellow gum (0.100 g, 41%).

(Z)-4-(3-(4-Bromo-3,5-dichlorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N-(1-((2,2,2-trifluoroethyl)carbamoyl)cyclopropyl)-2-(trifluoromethyl)benzamide(F60)

Isolated as a yellow gum (0.110 g, 39%).

(Z)-4-(3-(3,5-Dichloro-4-vinylphenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)-2-(trifluoromethyl)benzamide(F61)

Isolated as an off-white solid (0.089 g, 38%).

4-((Z)-3-(4-Chloro-3,5-dimethylphenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N—((R)-1-oxo-1-((2,2,2-trifluoroethyl)amino)propan-2-yl)-2-(trifluoromethyl)benzamide(F69)

Isolated as a pale yellow solid (0.120 g, 44%).

(Z)-4-(3-(4-Chloro-3,5-dimethylphenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N-(1-((2,2,2-trifluoroethyl)carbamoyl)cyclopropyl)-2-(trifluoromethyl)benzamide(F70)

Isolated as a pale yellow solid (0.110 g, 36%).

(Z)-4-(3-(4-Chloro-3,5-dimethylphenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)-2-(trifluoromethyl)benzamide(F71)

Isolated as a white solid (0.150 g, 51%).

4-((Z)-3-(3,5-Dichlorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N—((R)-1-(methyl(2,2,2-trifluoroethyl)amino)-1-oxopropan-2-yl)-2-(trifluoromethyl)benzamide(F72)

Isolated as a yellow gum (0.110 g, 40%).

4-((Z)-3-(3,4-Dichlorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N—((R)-1-(methyl(2,2,2-trifluoroethyl)amino)-1-oxopropan-2-yl)-2-(trifluoromethyl)benzamide(F73)

Isolated as a yellow gum (0.130 g, 47%).

(Z)-4-(3-(3,4-Dichlorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N-(2-(methyl(2,2,2-trifluoroethyl)amino)-2-oxoethyl)-2-(trifluoromethyl)benzamide(F74)

Isolated as a yellow gum (0.170 g, 63%).

(Z)-4-(3-(4-Bromo-3,5-dichlorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N-(2-(methyl(2,2,2-trifluoroethyl)amino)-2-oxoethyl)-2-(trifluoromethyl)benzamide(F75)

Isolated as a yellow gum (0.130 g, 53%).

4-((Z)-3-(4-Bromo-3,5-dichlorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N—((R)-1-(methyl(2,2,2-trifluoroethyl)amino)-1-oxopropan-2-yl)-2-(trifluoromethyl)benzamide(F76)

Isolated as a brown gum (0.115 g, 44%).

(Z)-4-(3-(3,5-Dibromo-4-chlorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N-(2-(methyl(2,2,2-trifluoroethyl)amino)-2-oxoethyl)-2-(trifluoromethyl)benzamide(F77)

Isolated as a yellow gum (0.112 g, 3%).

4-((Z)-3-(3,5-Dibromo-4-chlorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N—((R)-1-(methyl(2,2,2-trifluoroethyl)amino)-1-oxopropan-2-yl)-2-(trifluoromethyl)benzamide(F78)

Isolated as a yellow gum (0.135 g, 37%).

(Z)-4-(3-(3,4-Dibromophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N-(1-((2,2,2-trifluoroethyl)carbamoyl)cyclopropyl)-2-(trifluoromethyl)benzamide(F80)

Isolated as a pale yellow solid (0.127 g, 47%).

(Z)-4-(3-(3,5-Dichloro-4-vinylphenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N-(2-(methyl(2,2,2-trifluoroethyl)amino)-2-oxoethyl)-2-(trifluoromethyl)benzamide(F85)

Isolated as an off-white solid (0.110 g, 46%).

4-((Z)-3-(3,5-Dichloro-4-vinylphenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N—((R)-1-(methyl(2,2,2-trifluoroethyl)amino)-1-oxopropan-2-yl)-2-(trifluoromethyl)benzamide(F86)

Isolated as an off-white solid (0.140 g, 57%).

4-((Z)-3-(4-Chloro-3,5-dimethylphenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N—((R)-1-(methyl(2,2,2-trifluoroethyl)amino)-1-oxopropan-2-yl)-2-(trifluoromethyl)benzamide(F102)

Isolated as a white solid (0.130 g, 39%).

(Z)-4-(3-(4-Chloro-3,5-dimethylphenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N-(2-(methyl(2,2,2-trifluoroethyl)amino)-2-oxoethyl)-2-(trifluoromethyl)benzamide(F103)

Isolated as a white solid (0.170 g, 52%).

4-((Z)-3-(3,5-Dichlorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N—((R)-1-oxo-1-((2,2,2-trifluoroethyl)amino)propan-2-yl)-2-(trifluoromethyl)benzamide(F105)

Isolated as a yellow gum (0.115 g, 55%).

(Z)-4-(3-(3,5-Dibromophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N-(1-(methyl(2,2,2-trifluoroethyl)carbamoyl)cyclopropyl)-2-(trifluoromethyl)benzamide(F108)

Isolated as a pale yellow gum (0.103 g, 39%).

4-((Z)-3-(3-Bromo-5-chlorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N—((R)-1-oxo-1-((2,2,2-trifluoroethyl)amino)propan)-2-yl)-2-(trifluoromethyl)benzamide(F109)

Isolated as a yellow gum (0.115 g, 55%).

(Z)-4-(3-(4-Bromo-5-chlorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)-2-(trifluoromethyl)benzamide(F110)

Isolated as a brown solid (0.115 g, 53%).

(Z)-4-(3-(3,5-Dichloro-4-vinylphenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N-(1-(methyl(2,2,2-trifluoroethyl)carbamoyl)cyclopropyl)-2-(trifluoromethyl)benzamide(F111)

Isolated as a yellow gummy solid (0.075 g, 30%).

(Z)-4-(3-(3,5-Dichloro-4-vinylphenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N-(1-((2,2,2-trifluoroethyl)carbamoyl)cyclopropyl)-2-(trifluoromethyl)benzamide(F113)

Isolated as a pale yellow gum (0.085 g, 35%).

(Z)-4-(3-(3,5-Dichloro-4-fluorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N-(1-(methyl(2,2,2-trifluoroethyl)carbamoyl)cyclopropyl)-2-(trifluoromethyl)benzamide(F114)

Isolated as a pale yellow gum (0.100 g, 32%).

(Z)-4-(3-(3,5-Dichlorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N-(1-(methyl(2,2,2-trifluoroethyl)carbamoyl)cyclopropyl)-2-(trifluoromethyl)benzamide(F115)

Isolated as an orange gum (0.085 g, 26%).

(Z)-4-(3-(3-Bromo-5-chlorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N-(1-((2,2,2-trifluoroethyl)carbamoyl)cyclopropyl)-2-(trifluoromethyl)benzamide(F116)

Isolated as a brown gum (0.120 g, 56%).

(Z)-4-(3-(4-Bromo-3,5-dichlorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N-(1-(methyl(2,2,2-trifluoroethyl)carbamoyl)cyclopropyl)-2-(trifluoromethyl)benzamide(F117)

Isolated as a yellow gum (0.085 g, 36%).

(Z)-4-(3-(4-Dibromo-4-chlorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N-(1-(methyl(2,2,2-trifluoroethyl)carbamoyl)cyclopropyl)-2-(trifluoromethyl)benzamide(F118)

Isolated as a yellow gum (0.092 g, 30%).

(Z)-4-(3-(4-Chloro-3,5-dimethylphenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N-(1-(methyl(2,2,2-trifluoroethyl)carbamoyl)cyclopropyl)-2-(trifluoromethyl)benzamide(F119)

Isolated as a yellow solid (0.085 g, 20%).

(Z)-4-(3-(3,4-Dichlorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N-(1-(methyl(2,2,2-trifluoroethyl)carbamoyl)cyclopropyl)-2-(trifluoromethyl)benzamide(F120)

Isolated as a yellow solid (0.110 g, 34%).

4-((Z)-3-(3-Bromo-5-chlorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N—((R)-1-oxo-1-((2,2,2-trifluoroethyl)amino)propan-2-yl)-2-(trifluoromethyl)benzamide(F121)

Isolated as a yellow gum (0.115 g, 55%).

(Z)-4-(3-(3-Bromo-5-chlorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)-2-(trifluoromethyl)benzamide(F122)

Isolated as a yellow gum (0.110 g, 52%).

(Z)-4-(3-(3,4-Dibromophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N-(1-(methyl(2,2,2-trifluoroethyl)carbamoyl)cyclopropyl)-2-(trifluoromethyl)benzamide(F130)

Isolated as a yellow gum (0.157 g, 60%).

(Z)-4-(3-(3-Chloro-4-fluorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N-(1-((2,2,2-trifluoroethyl)carbamoyl)cyclopropyl)-2-(trifluoromethyl)benzamide(F131)

Isolated as a yellow gum (0.120 g, 41%).

(Z)-4-(3-(3,5-Dichlorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N-(1-(methyl(2,2,2-trifluoroethyl)carbamoyl)cyclopropyl)-2-(trifluoromethyl)benzamide(F133)

Isolated as an orange gum (0.080 g, 26%).

(Z)-4-(3-(4-Chloro-3,5-dimethylphenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N-(1-(methyl(2,2,2-trifluoroethyl)carbamoyl)cyclopropyl)-2-(trifluoromethyl)benzamide(F134)

Isolated as a yellow solid (0.085 g, 27%).

(Z)-4-(3-(3,4-Dichlorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N-(1-(methyl(2,2,2-trifluoroethyl)carbamoyl)cyclopropyl)-2-(trifluoromethyl)benzamide(F135)

Isolated as a yellow solid (0.110 g, 38%).

(Z)-4-(3-(4-Chloro-3-fluorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N-(1-((2,2,2-trifluoroethyl)carbamoyl)cyclopropyl)-2-(trifluoromethyl)benzamide(F136)

Isolated as a yellow solid (0.160 g, 53%).

(Z)-4-(3-(3-Bromo-5-chlorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N-(2-(methyl(2,2,2-trifluoroethyl)amino)-2-oxoethyl)-2-(trifluoromethyl)benzamide(F137)

Isolated as a brown gum (0.120 g, 52%).

4-((Z)-3-(3-Bromo-4-chlorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N—((R)-1-oxo-1-((2,2,2-trifluoroethyl)amino)propan-2-yl)-2-(trifluoromethyl)benzamide(F138)

Isolated as an off-white solid (0.112 g, 51%).

(Z)-4-(3-(3-Bromo-4-chlorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N-(1-((2,2,2-trifluoroethyl)carbamoyl)cyclopropyl)-2-(trifluoromethyl)benzamide(F139)

Isolated as an off-white solid (0.110 g, 51%).

Example 17: Preparation ofN—((R)-1-oxo-1-((2,2,2-trifluoroethyl)amino)propan-2-yl)-4-((E)-1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide(F17)

In an NMR tube,N—((R)-1-oxo-1-((2,2,2-trifluoroethyl)amino)propan-2-yl)-4-((Z)-1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide(F2) (0.05 g, 0.077 mmol) was dissolved into acetone-d₆. The reactionvessel was set up in a UV chamber and irradiated for 7 days. Thereaction mixture was concentrated. Purification by flash columnchromatography provided the title compound as a colorless oil (0.015 g,30%).

Example 18: Preparation ofN—((R)-1-oxo-1-((2,2,2-trifluoroethyl)amino)propan-2-yl)-4-((E)-1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide(F57)

tert-Butyl2-((2R)-2-(4-((Z)-1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamido)propanoyl)-2-(2,2,2-trifluoroethyl)hydrazinecarboxylate (F55) (0.150 g,0.197 mmol) was dissolved in dichloromethane (5 mL). Hydrogen chloride(2 M in diethyl ether, 1-2 mL) was added and the reaction mixture wasstirred at room temperature for 3 days. The reaction mixture wasconcentrated and the residue was taken up in diethyl ether and washedwith aqueous sodium bicarbonate, dried over magnesium sulfate, filtered,and concentrated. Purification by flash column chromatography using 2%acetone/dichloromethane as eluent provided the title compound as a whitefoam (0.0620 g, 48%).

Example 19: Preparation of(Z)-5-(4-(1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)phenyl)-6-oxa-4-azaspiro[2.4]hept-4-en-7-one(C55)

To a 25 mL round-bottomed flask was added(Z)-1-(4-(1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamido)cyclopropanecarboxylicacid (C57) (0.250 g, 0.432 mmol) in dichloromethane (4 mL) to give ayellow solution. 2,2,2-Trifluoroacetic anhydride (0.120 mL, 0.864 mmol)was then added and the reaction mixture was stirred at room temperatureovernight. Following concentration, the mixture was purified by flashcolumn chromatography to provide the title compound as a yellow oil(0.0780 g, 30%): ¹H NMR (400 MHz, CDCl₃) δ 8.04-7.96 (m, 2H), 7.85 (dd,J=8.1, 1.9 Hz, 1H), 7.44 (s, 2H), 5.90 (dd, J=32.5, 9.6 Hz, 1H), 4.62(p, J=8.8 Hz, 1H), 2.00-1.94 (m, 2H), 1.89-1.85 (m, 2H); ¹⁹F NMR (376MHz, CDCl₃) δ −59.53, −69.26 (d, J=2.4 Hz), −112.22; ESIMS m/z 560([M−H]⁻).

The following compounds were prepared according to the proceduresdisclosed in Example 19:

(Z)-5-(2-Methyl-4-(1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)phenyl)-6-oxa-4-azaspiro[2.4]hept-4-en-7-one(C56)

Isolated as a yellow foam (0.100 g, 53%): ¹H NMR (400 MHz, CDCl₃) δ7.98-7.88 (m, 1H), 7.51-7.45 (m, 2H), 7.44 (s, 2H), 5.79 (dd, J=32.8,9.6 Hz, 1H), 4.60 (p, J=8.9 Hz, 1H), 2.67 (s, 3H), 1.96-1.87 (m, 2H),1.87-1.78 (m, 2H); ¹⁹F NMR (376 MHz, CDCl₃) δ −69.39 (d, J=2.4 Hz),−112.11; ESIMS m/z 506 ([M−H]⁻).

Example 20: Preparation of(Z)-1-(4-(1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamido)cyclopropanecarboxylicacid (C57)

To a 250 mL round-bottomed flask was added(Z)-4-(1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzoylchloride (C23) (0.037 g, 0.072 mmol) and tetrahydrofuran (53 mL).N,N,N-Trimethyl-1-dodecanaminium bromide (0.0022 mg, 0.0072 mmol),sodium carbonate (0.012 g, 0.011 mmol), and1-aminocyclopropanecarboxylic acid hydrochloride (0.020 g, 0.144 mmol)were all added and the reaction mixture was stirred overnight at reflux.The reaction mixture was cooled to room temperature and the solidresidue filtered. The filtrate was concentrated to provide the titlecompound as a colorless oil which was used directly in the next step(0.038 g, 83%): ¹H NMR (300 MHz, Methanol-d₄) δ 8.01 (d, J=9.5 Hz, 2H),7.85 (d, J=8.0 Hz, 1H), 7.78 (s, 2H), 6.45 (dd, J=34.1, 9.8 Hz, 1H),4.97 (s, 1H), 1.49 (q, J=4.5 Hz, 2H), 1.08 (q, J=4.4 Hz, 2H); 19F NMR(376 MHz, CDCl₃) δ −60.81, −69.45, −111.92; ESIMS m/z 576 ([M−H]⁻).

The following compounds were prepared according to the proceduresdisclosed in Example 20:

(Z)-1-(2-Methyl-4-(1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzamido)cyclopropanecarboxylicacid (C58)

Isolated (0.140 g, 67%): ESIMS m/z 524 ([M−H]⁻).

Example 21: Preparation of (R)—N-allyl-2-aminopropanamide hydrochloride(C59)

(R)-tert-Butyl (1-(allylamino)-1-oxopropan-2-yl)carbamate (C65) (3.30 g,14.5 mmol) was taken up in dichloromethane (15 mL) and treated withhydrogen chloride (4 M in dioxane, 15.0 mL, 60.0 mmol). The reactionmixture was stirred at room temperature for 4 hours. The reactionmixture was concentrated and the residue was suspended indichloromethane. Concentration in vacuo provided the title compound as awhite solid (2.42 g, quant): mp 143-153° C.; ¹H NMR (400 MHz, DMSO-d₆) δ8.71 (t, J=5.9 Hz, 1H), 8.37-8.18 (m, 3H), 5.80 (ddd, J=15.7, 10.7, 5.1Hz, 1H), 5.13 (dd, J=32.1, 13.8 Hz, 2H), 3.85 (t, J=6.2 Hz, 1H), 3.75(d, J=4.8 Hz, 2H), 1.38 (d, J=6.9 Hz, 3H); ¹³C NMR (101 MHz, DMSO-d₆) δ169.21, 134.48, 115.30, 48.08, 40.74, 17.24; IR (thin film) 3213, 3073,3026, 2855, 1649, 1609 cm⁻¹.

The following compounds were prepared according to the proceduresdisclosed in Example 21:

(R)-2-Amino-N-(2-cyclopropylethyl)propanamide hydrochloride (C60)

Isolated as a gum (3.39 g, 100%): ¹H NMR (400 MHz, DMSO-d₆) δ 8.56 (t,J=5.6 Hz, 1H), 8.25 (s, 3H), 3.79 (m, 1H), 3.24-3.08 (m, 2H), 1.34 (d,J=7.0 Hz, 3H), 1.33-1.28 (m, 2H), 0.68 (q, J=6.8, 6.3 Hz, 1H), 0.38 (d,J=8.0 Hz, 2H), 0.02 (d, J=5.5 Hz, 2H); ¹³C NMR (101 MHz, DMSO-d₆) δ169.06, 48.11, 38.94, 33.72, 17.19, 8.45, 4.07; IR (thin film) 2916,1661, 1560, 1490, 1255, 1117 cm⁻¹.

(R)-2-Amino-N-(2-cyclopropylethyl)propanamide hydrochloride (C61)

Isolated as an off-white solid (0.624 g, quant): ¹H NMR (400 MHz,Methanol-d₄) δ rotamers 4.40 (q, J=7.0 Hz, 1H), 4.29-4.12 (m, 1H), 3.97(dq, J=15.2, 9.1 Hz, 1H), major, 3.12 (s, 3H), minor 2.99 (s, 3H), major1.40 (d, J=7.0 Hz, 3H), minor 1.38 (d, J=7.2 Hz, 3H).

(R)-2-Amino-N-ethyl-N-(2,2,2-trifluoroethyl)propanamide hydrochloride(C62)

Isolated as a gum (0.194 g, 92%): mp 148-151° C.; ¹H NMR (400 MHz,DMSO-d₆) δ rotamers 8.59 (s, 2H), 4.46-4.37 (m, 1H), 4.32-4.27 (m, 1H),4.16-3.93 (m, 1H), 3.62-3.53 (m, 1H), 3.45-3.33 (m, 2H), major 1.38 (d,J=6.8 Hz, 3H), minor 1.32 (d, J=6.7 Hz, 3H), major 1.19 (t, J=7.0 Hz,3H), minor 1.06 (t, J=7.0 Hz, 3H); ¹³C NMR (101 MHz, DMSO-d₆) δ rotamersmajor 171.03, minor 170.59, 124.76 (q, J_(CF)=281.1 Hz), 54.91, minor47.23 (q, J_(CF)=32.3 Hz), 45.82, 45.48, major 44.60 (q, J_(CF)=32.3Hz), 42.62, 16.66, 13.70, 11.83; ¹⁹F NMR (376 MHz, DMSO-d₆) δ −68.42,−69.10.

(R)-2-Amino-N-(2,2-difluoroethyl)propanamide hydrochloride (C63)

Isolated as a gum (0.194 g, 92%): ¹H NMR (400 MHz, DMSO-d₆) δ 8.98 (t,J=6.0 Hz, 1H), 8.36 (s, 3H), 6.06 (tt, J=55.6, 3.6 Hz, 1H), 3.88 (q,J=6.9 Hz, 1H), 3.71-3.39 (m, 2H), 1.38 (d, J=7.0 Hz, 3H); ¹⁹F NMR (376MHz, DMSO-d₆) δ −122.15.

(R)-2-Amino-N-(2,2,2-trifluoroethyl)butanamide hydrochloride (C64)

Isolated as a white solid (2.17 g, quant): mp 162-173° C.; ¹H NMR (400MHz, DMSO-d₆) δ 9.33 (t, J=6.3 Hz, 1H), 8.40 (s, 3H), 4.19-4.01 (m, 1H),3.93 (dt, J=10.7, 5.5 Hz, 1H), 3.87-3.76 (m, 1H), 1.79 (ddt, J=21.3,14.1, 7.1 Hz, 2H), 0.88 (t, J=7.5 Hz, 3H); ¹⁹F NMR (471 MHz, DMSO-d₆)5-70.64 (t, J=9.8 Hz); IR (thin film) 3348, 2887, 1674, 1601, 1157 cm⁻¹.

1-(1-Aminocyclopropyl)-4,4,4-trifluoro-butan-1-one hydrochloride (C65)

Isolated as a tan solid (0.296 g, 93%): mp 119-140° C.; ¹H NMR (400 MHz,Methanol-d₄) δ 2.71-2.37 (m, 4H), 1.84 (d, J=6.8 Hz, 2H), 1.55 (d, J=7.3Hz, 2H); ¹³C NMR (101 MHz, Methanol-d₄) δ 203.26, 129.13 (q,J_(CF)=275.5 Hz), 43.93, 29.45 (q, J_(CF)=29.8 Hz), 29.02, 15.24; ¹⁹FNMR (376 MHz, Acetone-d₆) δ 108.19.

1-Amino-N-methyl-N-(2,2,2-trifluoroethyl)cyclopropanecarboxamidehydrochloride (C66)

Isolated as an off white solid (2.83 g, 90%): mp 145-155° C.; ¹H NMR(500 MHz, DMSO-d₆) δ 9.29 (s, 3H), 4.22 (q, J=9.5 Hz, 2H), 3.25 (s, 3H),1.50-1.40 (m, 2H), 1.23-1.14 (m, 2H); ¹³C NMR (126 MHz, DMSO-d₆) δ166.62, 124.20 (q, J_(CF)=281.1 Hz), 47.73 (q, J_(CF)=32.8 Hz), 36.27,33.89, 10.36; ¹⁹F NMR (471 MHz, DMSO-d₆) δ −68.16 (t, J=9.5 Hz).

(R)—N-(Allyloxy)-2-amino-N-(2,2,2-trifluoroethyl)propanamidehydrochloride (C67)

Isolated as a glassy oil (0.120 g, 87%).

Example 22: Preparation of (R)-tert-butyl(1-(allylamino)-1-oxopropan-2-yl)carbamate (C68)

(R)-2-((tert-Butoxycarbonyl)amino)propanoic acid (5.26 g, 27.8 mmol) indichloromethane (40 mL) in a round-bottomed flask was placed in a roomtemperature water bath. 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide(5.91 g, 30.3 mmol) was added followed by allyl amine (4.00 mL, 53.5mmol) in 0.5 mL portions. 4-Dimethylaminopyridine (3.70 g, 30.3 mmol)was added, and the reaction mixture was stirred for 18 hours at roomtemperature while under a drying tube charged with calcium sulfate. Thereaction mixture was washed with hydrochloric acid (10%, 3×). Theorganic layer was diluted with a dichloromethane (100 mL) and ethylacetate (250 mL), washed with saturated sodium bicarbonate and saturatedsodium chloride, dried over magnesium sulfate, filtered, andconcentrated providing the title compound as a white solid (3.51 g,55%): [a]³+30.60 (c 0.00620, dichloromethane); mp 87-94° C.; ¹H NMR (400MHz, CDCl₃) δ 6.40 (s, 1H), 5.91-5.75 (m, 1H), 5.25-5.09 (m, 2H), 5.07(s, 1H), 4.19 (d, J=10.6 Hz, 1H), 3.88 (t, J=5.8 Hz, 2H), 1.44 (s, 9H),1.37 (d, J=7.1 Hz, 3H); EIMS m/z 228 ([M]⁺).

The following compounds were prepared according to the proceduresdisclosed in Example 22:

(R)-tert-Butyl (1-((2-cyclopropylethyl)amino)-1-oxopropan-2-yl)carbamate(C69)

Isolated (4.7 g, 71%): mp 67-69° C.; ¹H NMR (400 MHz, CDCl₃) δ 6.35 (s,1H), 5.05 (s, 1H), 4.14 (m, 1H), 3.34 (m, 2H), 1.44 (s, 9H), 1.40 (m,2H), 1.35 (d, J=7.1 Hz, 3H), 0.74-0.59 (m, 1H), 0.53-0.37 (m, 2H),0.14-0.03 (m, 2H); EIMS m/z 256 ([M]⁺).

(R)-tert-Butyl(1-(methyl(2,2,2-trifluoroethyl)amino)-1-oxopropan-2-yl)carbamate (C70)

Isolated as a white solid using 2,2,2-trifluoro-N-methylethanaminehydrochloride (0.388 g, 22%): [a]_(D) ²³−1.1° (c 0.00540,dichloromethane); mp 52-54° C.; ¹H NMR (400 MHz, CDCl₃) δ rotamers 5.38(d, J=8.4 Hz, 1H), 4.76-4.59 (m, 1H), 4.30 (dd, J=15.0, 9.1 Hz, 1H),3.89-3.65 (m, 1H), 3.20 (s, 3H), 1.43 (m, 9H), 1.33 (d, J=6.8 Hz, 3H);¹⁹F NMR (376 MHz, CDCl₃) δ rotamers −69.85, −70.62.

(R)-tert-Butyl (1-((2,2-difluoroethyl)amino)-1-oxopropan-2-yl)carbamate(C71)

Isolated as a white solid (3.30 g, 60%): mp 69-72° C.; ¹H NMR (400 MHz,CDCl₃) δ 6.78 (s, 1H), 5.83 (tt, J=56.0, 4.1 Hz, 1H), 5.00 (d, J=7.5 Hz,1H), 4.36-4.11 (m, 1H), 3.74-3.40 (m, 2H), 1.45 (s, 9H), 1.37 (d, J=7.1Hz, 3H); ¹⁹F NMR (376 MHz, CDCl₃) δ −123.02 (d, J=3.5 Hz); IR (thinfilm) 3334, 2924, 2853, 1670, 1598 cm⁻¹; EIMS m/z 179([M-Otert-butyl]⁺).

(R)-tert-Butyl(1-oxo-1-((2,2,2-trifluoroethyl)amino)butan-2-yl)carbamate (C72)

Isolated as a white solid (2.77 g, 83%): mp 110-114° C.; ¹H NMR (400MHz, CDCl₃) δ 7.50-7.29 (m, 1H), 5.32 (d, J=8.4 Hz, 1H), 4.16 (d, J=7.6Hz, 1H), 3.96 (m, 1H), 3.88-3.69 (m, 1H), 1.89-1.73 (m, 1H), 1.66 (m,1H), 1.44 (s, 9H), 0.95 (t, J=7.4 Hz, 3H); ¹³C NMR (101 MHz, CDCl₃) δ173.43, 156.09, 124.05 (q, J_(CF)=278.6 Hz), 80.10, 55.54, 40.39 (q,J_(CF)=34.7 Hz), 28.15, 25.90, 9.74; ¹⁹F NMR (471 MHz, CDCl₃) 5 rotamers−72.52, −73.29; EIMS m/z 229 ([M]⁺).

Example 23: Preparation of (R)-tert-butyl(1-(ethyl(2,2,2-trifluoroethyl)amino)-1-oxopropan-2-yl)carbamate (C73)

To a 20 mL vial containing a solution of(R)-2-((tert-butoxycarbonyl)amino)propanoic acid (0.489 g, 2.58 mmol) indichloromethane (5 mL) cooled to 0° C. was added2,2,2-trifluoro-N-ethylethanamine hydrochloride (0.384 g, 2.35 mmol),1H-benzo[d][1,2,3]triazol-1-ol hydrate (0.360 g, 2.35 mmol),diisopropylethylamine (1.00 mL, 5.16 mmol), and1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.495 g,2.58 mmol). The reaction was stirred for 2 days at room temperature. Thereaction mixture was diluted with diethyl ether, washed withhydrochloric acid (0.1 N), sodium bicarbonate (15%), and saturatedsodium chloride, dried over sodium sulfate, filtered, and concentrated.Purification by flash column chromatography using 0-100% ethylacetate/hexanes as eluent provided the title compound as a white solid(0.092 g, 12%): ¹H NMR (400 MHz, CDCl₃) δ 5.34 (d, J=8.7 Hz, 1H),4.73-4.60 (m, 1H), 4.39 (dq, J=15.0, 9.2 Hz, 1H), 3.80-3.43 (m, 3H),1.43 (d, J=5.2 Hz, 9H), 1.34 (d, J=6.8 Hz, 3H), 1.29 (q, J=6.9 Hz, 3H);¹⁹F NMR (376 MHz, CDCl₃) δ −69.65, −70.65; ESIMS m/z 242([M-tert-butyl]⁻).

Example 24: Preparation of tert-butyl2-(2,2,2-trifluoroethyl)hydrazinecarboxylate (C74)

A 100 mL round-bottomed flask was charged with(2,2,2-trifluoroethyl)hydrazine (2.0 g, 12 mmol) and methanol (15 mL)and stirred at room temperature. Di-tert butyl dicarbonate (2.7 g, 12mmol) was added in several portions. The reaction mixture was stirred atroom temperature for 18 hours. The reaction mixture was concentratedproviding the title compound as a white solid (2.3 g, 87%): ¹H NMR (300MHz, CDCl₃) δ 6.24 (s, 1H), 4.23 (s, 1H), 3.41 (qd, J=9.3, 4.6 Hz, 2H),1.47 (s, 9H).

Example 25: Preparation of (R)-tert-butyl2-(2-(((benzyloxy)carbonyl)amino)propanoyl)-2-(2,2,2-trifluoroethyl)hydrazinecarboxylate(C75)

To a solution of (R)-2-((benzyloxy)carbonyl)amino)propanoic acid (0.500g, 2.24 mmol) in dry dichloromethane (10 mL) was added1-chloro-N,N,2-trimethyl-1-propenylamine (0.359 g, 2.69 mmol) indichloromethane via pipette at 0° C. The reaction mixture was stirredfor 10 minutes. A pre-mixed solution of pyridine (0.213 g, 2.69 mmol)and tert-butyl 2-(2,2,2-trifluoroethyl)hydrazinecarboxylate (C71) (0.480g, 2.24 mmol) was added via pipette. The reaction mixture was stirred at0° C. to room temperature overnight. The reaction mixture was dilutedwith dichloromethane and added to dilute aqueous hydrochloric acid. Thelayers were separated and the aqueous layer was extracted withdichloromethane (2×) and discarded. The combined organic layers werewashed with saturated aqueous sodium bicarbonate (2×), dried overmagnesium sulfate, filtered, and concentrated. Purification by flashcolumn chromatography using 15-20% ethyl acetate/hexanes as eluentprovided the title compound as a pale thick oil (0.820 g, 87%): ¹H NMR(300 MHz, CDCl₃) δ 7.34 (s, 5H), 6.77 (s, 1H), 5.42 (s, 1H), 5.09 (s,2H), 4.83 (m, 2H), 3.55 (d, J=33.0 Hz, 1H), 1.50 (s, 9H), 1.32 (d, J=6.8Hz, 3H); ¹⁹F NMR (376 MHz, CDCl₃) δ rotamers −69.70, −70.12.

Example 26: Preparation of (R)-tert-butyl2-(2-aminopropanoyl)-2-(2,2,2-trifluoroethyl)hydrazinecarboxylate (C76)

(R)-tert-Butyl2-(2-(((benzyloxy)carbonyl)amino)propanoyl)-2-(2,2,2-trifluoroethyl)hydrazinecarboxylate(C72) (0.820 g, 1.96 mmol) was dissolved in ethanol (10 mL) andpalladium on carbon (5%, catalytic amount) was added. The reaction wasshaken under a hydrogen atmosphere at room temperature for 18 hours. Thereaction mixture was filtered through a pad of Celite® and the pad waswashed several times with ethanol. The combined ethanol wasconcentrated. The residue was taken up in dichloromethane, washedrepeatedly with saturated sodium chloride, dried over magnesium sulfate,filtered, and concentrated to provide the title compound as a glassy oil(0.400 g, 72%): ESIMS m/z 286 ([M+H]⁺).

Example 27: Preparation of tert-butylN-[1-(4,4,4-trifluorobutanoyl)cyclopropyl]carbamate (C77)

To a solution of 3,3,3-trifluoropropyl magnesium bromide (0.5 M, 30.0mL, 15.0 mmol) in tetrahydrofuran in an oven-dried round-bottomed flaskunder a nitrogen atmosphere was added tert-butyl(1-(methoxy(methyl)carbamoyl)cyclopropyl)carbamate (1.01 g, 4.12 mmol)in tetrahydrofuran (5.00 mL). The mixture was stirred at roomtemperature for 20 hours and then quenched with aqueous sodium bisulfate(5%). The mixture was extracted ethyl acetate and the organic phasewashed with saturated sodium chloride, dried over magnesium sulfate,filtered, and concentrated. Purification by flash column chromatographyusing ethyl acetate/hexanes as eluent provided the title compound as awhite solid (0.826 g, 71%): mp 71-93° C.; ¹H NMR (400 MHz, CDCl₃) δ 5.20(s, 1H), 2.95 (t, J=7.8 Hz, 2H), 2.50-2.20 (m, 2H), 1.63-1.57 (m, 2H),1.47 (s, 9H), 1.22-1.14 (m, 2H); ¹⁹F NMR (376 MHz, CDCl₃) δ −66.64; EIMSm/z 225 ([(M+H)-(tert-butyl)]⁺).

Example 28: Preparation of tert-butyl(1-(methyl(2,2,2-trifluoroethyl)carbamoyl)cyclopropyl)carbamate (C78)

To a mixture of 1-((tert-butoxycarbonyl)amino)cyclopropanecarboxylicacid (3.00 g, 14.9 mmol) and 2,2,2-trifluoro-N-methylethanaminehydrochloride (2.23 g, 14.9 mmol) in dichloromethane (40 mL) was addeddiisopropylethylamine (6.51 mL, 37.3 mmol) followed by ((1H-benzo[d][1,2, 3]triazol-1-yl)oxy)tri(pyrrolidin-1-yl)phosphoniumhexafluorophosphate(V) (7.76 g, 14.9 mmol). The reaction mixture wasstirred at room temperature for 2 hours. The reaction mixture wasdiluted with ethyl acetate and washed with aqueous hydrochloric acid(0.5 M) followed by a saturated aqueous sodium bicarbonate wash. Theorganic layer was dried over sodium sulfate, filtered, and concentrated.Purification by flash column chromatography provided the title compoundas an off-white solid (3.60 g, 73%): 109-112° C.; ¹H NMR (400 MHz,DMSO-d₆) δ 7.73 (s, 1H), 4.31-4.03 (m, 2H), 3.22-3.01 (m, 3H), 1.35 (d,J=13.0 Hz, 9H), 1.15 (t, J=4.0 Hz, 2H), 0.87 (q, J=4.7 Hz, 2H); ¹³C NMR(126 MHz, CDCl₃) δ 171.72, 154.93, 124.79 (q, J_(CF)=280 Hz), 80.32,49.73 (q, J_(CF)=34.00 Hz), 37.00, 35.47, 28.15, 15.43; ¹⁹F NMR (471MHz, CDCl₃) δ rotamers −69.41, −69.73.

Example 29: Preparation of (R)-benzyl(1-(methoxyamino)-1-oxopropan-2-yl)carbamate (C79)

(R)-2-(((Benzyloxy)carbonyl)amino)propanoic acid (0.500 g, 2.24 mmol) intetrahydrofuran/water (2:1, 15 mL) was treated with1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (0.472 g, 2.46 mmol),O-methylhydroxylamine hydrochloride (0.224 g, 2.69 mmol), andtriethylamine (0.272 g, 2.69 mmol). The reaction mixture was stirred for18 hours, then concentrated. The residue was partitioned betweendichloromethane and dilute aqueous hydrochloric acid. The aqueous phasewas extracted with dichloromethane. The combined organic layers werewashed with aqueous sodium bicarbonate, dried over magnesium sulfate,filtered, and concentrated providing the title compound as a white solid(0.250 g, 44%): mp 109-110° C.; ¹H NMR (400 MHz, CDCl₃) δ 9.01 (s, 1H),7.35 (m, 5H), 5.10 (m, 3H), 4.12 (s, 1H), 3.75 (s, 3H), 1.39 (d, J=7.0Hz, 3H); ESIMS m/z 253 ([M+H]⁺).

Example 30: Preparation of (R)-benzyl(1-(methoxy(2,2,2-trifluoroethyl)amino)-1-oxopropan-2-yl)carbamate (C80)

A mixture of (R)-benzyl (1-(methoxyamino)-1-oxopropan-2-yl)carbamate(C79) (0.300 g, 1.19 mmol), potassium carbonate (0.329 g, 2.38 mmol),and anhydrous tetrahydrofuran (15 mL) was treated with2,2,2-trifluoroethyl trifluoromethanesulfonate (0.552 g, 2.38 mmol). Theresulting mixture was stirred at room temperature for 18 hours, thenpartitioned between water and diethyl ether. The aqueous phase wasextracted with diethyl ether (2×). The combined organic layers werewashed with saturated sodium chloride, dried over magnesium sulfate,filtered, and concentrated. Purification by flash column chromatographyusing 1% acetone/dichloromethane as eluent provided the title compoundas a clear oil (0.150 g, 38%): ¹H NMR (400 MHz, CDCl₃) δ 7.36 (d, J=3.7Hz, 5H), 5.43 (d, J=8.5 Hz, 1H), 5.11 (q, J=12.2 Hz, 2H), 4.78 (t, J=7.5Hz, 1H), 4.44 (dd, J=16.0, 8.4 Hz, 1H), 4.10-3.92 (m, 1H), 3.86 (s, 3H),1.38 (d, J=7.0 Hz, 3H); ¹⁹F NMR (376 MHz, CDCl₃) δ 20-69.31; ESIMS m/z335 ([M+H]⁺).

The following compound was prepared according to the procedure disclosedin Example 30:

(R)-tert-Butyl(1-((allyloxy)(2,2,2-trifluoroethyl)amino)-1-oxopropan-2-yl)carbamate(C81)

Isolated as a white solid (0.200 g, 30%): ¹H NMR (400 MHz, CDCl₃) δ6.08-5.89 (m, 1H), 5.49-5.31 (m, 2H), 5.14 (d, J=8.5 Hz, 1H), 4.71 (t,J=7.7 Hz, 1H), 4.52 (m, 3H), 4.03 (m, 1H), 1.44 (s, 9H), 1.35 (d, J=7.0Hz, 3H); ¹⁹F NMR (376 MHz, CDCl₃) δ −69.09.

Example 31: Preparation of(R)-2-amino-N-methoxy-N-(2,2,2-trifluoroethyl)propanamide hydrochloride(C82)

A solution of (R)-benzyl(1-(methoxy(2,2,2-trifluoroethyl)amino)-1-oxopropan-2-yl)carbamate (C80)(0.300 g, 0.897 mmol) in ethanol (10 mL) and hydrochloric acid (1 N, 1mL) in ethanol was treated with palladium on carbon (5%, catalyticamount). The reaction was shaken under hydrogen at room temperature for18 hours. The reaction mixture was filtered through a pad of Celite® andthe pad was washed several times with ethanol. The combined ethanolwashes were concentrated to provide the title compound as a beige foam(0.210 g, 99%): ¹H NMR (400 MHz, DMSO-d₆) δ 8.43 (s, 3H), 4.71 (dq,J=16.1, 9.3 Hz, 1H), 4.55 (dq, J=17.2, 8.8 Hz, 1H), 4.26 (q, J=7.2 Hz,1H), 3.82 (s, 3H), 1.38 (d, J=6.9 Hz, 3H); ¹⁹F NMR (376 MHz, DMSO-d₆) δ−68.12.

Example 32: Preparation ofN-methyl-2-(methylamino)-N-(2,2,2-trifluoroethyl)acetamide hydrochloride(C83)

To a mixture of(1-cyano-2-ethoxy-2-oxoethylidenaminooxy)dimethylamino-morpholino-carbeniumhexafluorophosphate (0.754 g, 1.76 mmol) and2-((tert-butoxycarbonyl)(methyl)amino)acetic acid (0.333 g, 1.76 mmol)dissolved in N,N-dimethylformamide (2 mL) was addeddiisopropylethylamine (1.40 mL, 8.02 mmol). The solution was stirred for15 minutes at room temperature then treated with2,2,2-trifluoro-N-methylethanamine hydrochloride (0.342 g, 2.29 mmol).After stirring overnight at room temperature, the mixture waspartitioned between water and ethyl acetate. The organic phase was driedover magnesium sulfate, concentrated, and purified by flash columnchromatography to afford a foam which was dissolved in dichloromethaneand treated with hydrogen chloride (4 M in dioxane, 0.750 mL, 3.00mmol). After standing overnight under a nitrogen atmosphere the solutionwas then concentrated to provide the title compound as a colorless foam(0.164 g, 38%): ¹H NMR (400 MHz, DMSO-d₆) δ 8.86 (s, 2H), 4.29 (dq,J=28.7, 9.3 Hz, 2H), 4.16 (s, 2H), 3.07 (s, 3H), 2.56 (s, 3H); ¹³C NMR(126 MHz, DMSO-d₆) δ 167.45, 125.23 (q, J_(CF)=281.2 Hz), 48.73, 47.59(q, J_(CF)=32.7 Hz), 35.72, 33.09; ¹⁹F NMR (376 MHz, Methanol-d₄) δrotamers −71.67, −71.68, −71.70.

Example 33: Preparation of (R)-tert-butyl(1-((allyloxy)amino)-1-oxopropan-2-yl)carbamate (C84)

To (R)-2-((tert-butoxycarbonyl)amino)propanoic acid (2.00 g, 10.6 mmol)in tetrahydrofuran (35 mL) was added2-chloro-4,6-dimethoxy-1,3,5-triazine (2.21 g, 12.6 mmol) and4-methylmorpholine (3.21 g, 31.7 mmol). The reaction mixture was stirredat room temperature for 1 hour then O-allylhydroxylamine hydrochloride(1.16 g, 10.6 mmol) was added. After stirring 18 hours water was addedand the mixture extracted with diethyl ether (3×). The combined etherlayer was washed with saturated aqueous carbonate (2×), aqueoushydrochloric acid (1 N), saturated sodium chloride, dried over magnesiumsulfate, filtered, and concentrated to provide the title compound as awhite solid (1.83 g, 71%): ¹H NMR (400 MHz, CDCl₃) δ 9.15 (s, 1H), 5.97(ddt, J=16.9, 10.3, 6.4 Hz, 1H), 5.33 (m, 2H), 5.00 (d, J=13.5 Hz, 1H),4.39 (m, 2H), 4.05 (d, J=12.8 Hz, 1H), 1.44 (s, 9H), 1.36 (d, J=7.0 Hz,3H).

Example 34: Preparation of3-amino-1-(2,2,2-trifluoroethyl)-piperidin-2-one hydrochloride (C85)

To a solution of tert-butyl (2-oxopiperidin-3-yl)carbamate (0.250 g,1.17 mmol) in 10 mL of anhydrous tetrahydrofuran, cooled in an ice-waterbath, was added sodium hydride (60% oil immersion, 0.0470 g, 1.17 mmol).After stirring 1 hour at ambient temperature 2,2,2-trifluoroethyltrifluoromethanesulfonate (0.284 g, 1.23 mmol) was added and theresulting mixture was stirred at room temperature for 20 hours. Themixture was partitioned between water and diethyl ether. The aqueousphase was extracted with diethyl ether (3×). The combined organic layerwas dried with magnesium sulfate, concentrated, and purified by flashcolumn chromatography using 2% acetone/dichloromethane as eluent toprovide a clear oil. The oil was taken up in dichloromethane (5 mL) andhydrogen chloride (2 N in diethyl ether, 1 mL). After stirring for 18hours, the mixture was concentrated to provide the title compound as awhite foam (0.0600 g, 26%): ¹H NMR (300 MHz, DMSO-d₆) δ 8.29 (s, 3H),4.47-4.14 (m, 2H), 4.00 (dd, J=11.6, 6.2 Hz, 1H), 3.64-3.41 (m, 2H),2.17 (m, 1H), 1.92 (m, 2H), 1.85-1.58 (m, 1H).

The following molecules in Table 1 may be prepared according to theprocedures disclosed: P1, P2, P3, P4, P5, P6, P7, P8, P9, P10, P11, P12,P13, P14, P15, P16, P17, P18, P19, P20, P21, P22, P23, P24, P25, P26,P27, P28, P29, P30, P31, P32, P33, P34, P35, P37, P39, P40, P41, P42,P43, P44, P45, P46, P47, P48, P49, P50, P51, P52, P53, P54, P55, P56,P57, P58, P59, P60, P61, P62, P63, P64, P65, P66, P67, P68, P69, P70,P71, P72, P73, P74, P75, P76, P77, P78, P79, P80, P81, P82, P83, P84,P85, P86, P87, P88, P89, P90, P91, P92, P93, P94, P95, P96, P97, P98,P99, P100, P101, P102, P103, and P104.

TABLE 1 Structure and Preparation Method for Prophetic Molecules No.Structure P1

P2

P3

P4

P5

P6

P7

P8

P9

P10

P11

P12

P13

P14

P15

P16

P17

P18

P19

P20

P21

P22

P23

P24

P25

P26

P27

P28

P29

P30

P31

P32

P33

P34

P35

P37

P39

P40

P41

P42

P43

P44

P45

P46

P47

P48

P49

P50

P51

P52

P53

P54

P55

P56

P57

P58

P59

P60

P61

P62

P63

P64

P65

P66

P67

P68

P69

P70

P71

P72

P73

P74

P75

P76

P77

P78

P79

P80

P81

P82

P83

P84

P85

P86

P87

P88

P89

P90

P91

P92

P93

P94

P95

P96

P97

P98

P99

P100

P101

P102

P103

P104

The following compounds were prepared in like manner to the procedureoutlined in Example 1:

(Z)-4-(1,4,4,4-Tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-1-naphthoicacid (C86)

Isolated as a yellow solid (0.85 g, 53%): ¹H NMR (300 MHz, CDCl₃) δ 8.30(d, J=7.5 Hz, 1H), 8.07-8.05 (m, 1H), 7.70-7.61 (m, 4H), 7.49 (s, 2H),5.69 (dd, J=9.9, 31.2 Hz, 1H), 4.75-4.69 (m, 1H); IR (thin film) 3445,1684, 1260, 750 cm⁻¹; ESIMS m/z 475.23 ([M]⁻).

(Z)-4-(3-(3-Chloro-5-(trifluoromethyl)phenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-2-(trifluoromethyl)benzoicacid (C87)

Isolated as a brown solid (1.0 g, 47%): ¹H NMR (300 MHz, DMSO-d₆) δ13.80 (s, 1H), 8.17-8.12 (m, 3H), 7.91-7.86 (m, 3H), 6.87 (dd, J=9.9,36.0 Hz, 1H), 5.39-5.32 (m, 1H); ESIMS m/z 493.14 ([M−H]⁻).

(Z)-4-(3-(3,4-Dichloro-5-methylphenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-2-(trifluoromethyl)benzoicacid (C88)

Isolated as a brown gum (1.7 g, 42%): ¹H NMR (300 MHz, DMSO-d₆) δ 13.80(s, 1H), 8.14 (s, 1H), 8.09 (d, J=8.1 Hz, 1H), 7.91 (d, J=8.1 Hz, 1H),7.83 (s, 1H), 7.65 (s, 1H), 6.87 (dd, J=9.9, 36.0 Hz, 1H), 5.13-5.07 (m,1H), 2.42 (s, 3H); IR (thin film) 3446, 2928, 1716 cm⁻¹; ESIMS m/z473.10 ([M−H]⁻).

(Z)-4-(3-(4-Bromo-3-chlorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-2-(trifluoromethyl)benzoicacid (C89)

Isolated as a brown gum (2.5 g, 68%): ¹H NMR (400 MHz, CDCl₃) δ 8.02 (d,J=8.4 Hz, 1H), 7.94 (s, 1H), 7.83 (d, J=7.2 Hz, 1H), 7.66 (d, J=8.4 Hz,1H), 7.50 (s, 1H), 7.17 (dd, J=2.0, 8.4 Hz, 1H), 5.96 (dd, J=9.2, 32.0Hz, 1H), 4.65-4.61 (m, 1H); IR (thin film) 3447, 2927, 1715, 750 cm⁻¹;ESIMS m/z 504.4 ([M−H]⁻).

(Z)-4-(3-(3-Bromo-4,5-dichlorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-2-(trifluoromethyl)benzoicacid (C90)

Isolated as a yellow gum (2.6 g, 27%): ¹H NMR (400 MHz, CDCl₃) δ 11.66(s, 1H), 8.04 (d, J=7.3 Hz, 1H), 7.97 (d, J=1.7 Hz, 1H), 7.84 (dd,J=8.2, 1.8 Hz, 1H), 7.60 (d, J=2.0 Hz, 1H), 7.49 (d, J=2.1 Hz, 1H), 5.91(dd, J=32.4, 9.6 Hz, 1H), 4.62 (p, J=8.8 Hz, 1H); ¹⁹F NMR (376 MHz,CDCl₃) δ −57.06, −66.85, −110.35; ESIMS m/z 540 ([M−H]⁻).

(Z)-4-(3-(4-Chloro-3-methylphenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-2-(trifluoromethyl)benzoicacid (C91)

Isolated as a brown gummy oil (0.45 g, 75%): ¹H NMR (300 MHz, DMSO-d₆) δ13.60 (br s, 1H), 7.98 (s, 1H) 7.92 (d, J=8.1 Hz, 1H), 7.90 (d, J=8.1Hz, 1H), 7.53-7.38 (m, 2H), 7.04 (dd, J=8.4, 15.6 Hz, 1H), 6.89 (d,J=15.9 Hz, 1H), 4.76-4.63 (m, 1H), 2.35 (s, 3H); IR (thin film) 3436,1727, 1150, 765 cm⁻¹; ESIMS m/z 420.79 ([M−H]⁻).

(Z)-2-Chloro-4-(1,4,4-trifluoro-3-(3,4,5-trichlorophenyl)pent-1-en-1-yl)benzoicacid (C92)

Isolated as a brown gum (1.5 g, 39%): ¹H NMR (400 MHz, CDCl₃) δ 7.87 (d,J=7.2 Hz, 1H), 7.66 (d, J=8.0 Hz, 1H), 7.41-7.35 (m, 3H), 5.96 (dd,J=10.0, 33.6 Hz, 1H), 4.98-4.96 (m, 1H), 1.67 (t, 1=19.2 Hz, 3H).

(Z)-4-(3-(3,5-Dichloro-4-(difluoromethyl)phenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-2-(trifluoromethyl)benzoicacid (C94)

Isolated as a yellow gum (0.45 g, 25%): ¹H NMR (400 MHz, DMSO-d₆) δ13.80 (s, 1H), 8.15 (s, 1H), 8.09 (dd, J=8.0 Hz, 1H), 8.00 (s, 2H), 7.92(d, J=8.4 Hz, 1H), 7.45 (t, J=12.9 Hz, 1H), 6.90 (dd, J=10.0, 35.6 Hz,1H), 5.33-5.31 (m, 1H); ESIMS m/z 509.11 ([M−H]⁻).

(Z)-4-(3-(3-Chloro-4-methoxyphenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-2-(trifluoromethyl)benzoicacid (C95)

Isolated as a yellow gum (0.46 g, 66%): ¹H NMR (400 MHz, CDCl₃) δ 7.98(d, J=8.4 Hz, 1H), 7.93 (s, 1H), 7.81 (d, J=8.0 Hz, 1H), 7.42 (s, 1H),7.26 (s, 1H), 6.95 (d, J=8.8 Hz, 1H), 5.96 (dd, J=10.0, 32.8 Hz, 1H),4.62-4.57 (m, 1H), 3.91 (s, 3H); ESIMS m/z 455.36 ([M−H]⁻).

(Z)-4-(3-(3-Chloro-4-ethylphenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-2-(trifluoromethyl)benzoicacid (C96)

Isolated as a yellow gum (0.60 g, 53%): ¹H NMR (400 MHz, DMSO-d₆) δ13.75 (br s, 1H), 8.15 (s, 1H), 8.01 (d, J=8.4 Hz, 1H), 7.90 (d, J=8.4Hz, 1H), 7.78 (d, J=8.4 Hz, 1H), 7.55 (d, J=8.4 Hz, 1H), 7.41 (d, J=8.0Hz, 1H), 6.87 (dd, J=9.6, 35.6 Hz, 1H), 5.08-5.04 (m, 1H), 2.73-2.67 (m,2H), 1.17 (t, J=6.0 Hz, 3H); ESIMS m/z 453.38 ([M−H]⁻).

(Z)-4-(3-(3-Chloro-4-(2,2,2-trifluoroethoxy)phenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-2-(trifluoromethyl)benzoicacid (C97)

Isolated as a brown solid (0.30 g, 53%): ¹H NMR (300 MHz, DMSO-d₆) δ13.90 (br s, 1H), 8.05-7.99 (m, 2H), 7.83-7.75 (m, 2H), 7.64-7.61 (m,1H), 7.34 (d, J=8.4 Hz, 1H), 6.81 (dd, J=9.9, 36.3 Hz, 1H), 5.08-4.82(m, 3H); IR (thin film) 3433, 2924, 1712, 749 cm⁻¹; ESIMS m/z 523.20([M−H]⁻).

(Z)-4-(1,4,4,4-Tetrafluoro-3-(4-fluoro-3-(trifluoromethyl)phenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzoicacid (C98)

Isolated as a brown gum (1.0 g, 42%): ¹H NMR (300 MHz, DMSO-d₆) δ 13.80(br s, 1H), 8.16 (s, 1H), 8.12-8.07 (m, 3H), 7.92 (d, J=8.7 Hz, 1H),7.66 (d, J=10.2 Hz, 1H), 6.96 (dd, J=9.9, 35.4 Hz, 1H), 5.36-5.29 (m,1H); IR (thin film) 2926, 1715, 765 cm⁻¹; ESIMS m/z 477.2 ([M−H]⁻).

(Z)-4-(1,4,4,4-Tetrafluoro-3-(3,4,5-trifluorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzoicacid (C99)

Isolated as a brown gum (0.8 g, 56%): ¹H NMR (300 MHz, DMSO-d₆) δ 13.98(br s, 1H), 8.14 (br s, 1H), 8.08-8.05 (m, 1H), 7.92-7.89 (m, 1H),7.77-7.72 (m, 2H), 6.85 (dd, J=9.9, 35.4 Hz, 1H), 5.23-5.16 (m, 1H); IR(thin film) 3100, 1715 cm⁻¹; ESIMS m/z 444.79 ([M−H]⁻).

(Z)-4-(3-(3-Chloro-4,5-difluorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-2-(trifluoromethyl)benzoicacid (C100)

Isolated as a brown gum (0.55 g, 56%): ¹H NMR (300 MHz, DMSO-d₆) δ 13.92(br s, 1H), 8.14 (s, 1H), 8.08 (d, J=8.1 Hz, 1H), 7.92-7.85 (s, 3H),6.87 (dd, J=9.9, 35.4 Hz, 1H), 5.24-5.18 (m, 1H); IR (thin film) 3085,1715, 659 cm⁻¹; ESIMS m/z 461.24 ([M−H]⁻).

(Z)-4-(3-(3-Chloro-5-fluorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-2-(trifluoromethyl)benzoicacid (C101)

Isolated as a brown gum (0.40 g, 63%): ¹H NMR (400 MHz, DMSO-d₆) δ 13.89(br s, 1H), 8.16 (s, 1H), 8.09 (d, J=8.4 Hz, 1H), 7.93-7.86 (m, 1H),7.69 (s, 1H), 7.63 (d, J=9.6 Hz, 1H), 7.52-7.49 (m, 1H), 6.87 (dd,J=10.4, 35.6 Hz, 1H), 5.23-5.18 (m, 1H); IR (thin film) 2924, 1698, 1258cm⁻¹; ESIMS m/z 442.80 ([M−H]⁻).

(Z)-4-(3-(4-Bromo-3-fluorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-2-(trifluoromethyl)benzoicacid (C102)

Isolated as a dark brown oil (0.130 g, 28%): ¹H NMR (300 MHz, CDCl₃) δ7.87 (m, 2H), 7.74 (d, J=8.1 Hz, 1H), 7.58 (dd, J=8.3, 7.1 Hz, 1H), 7.18(dd, J=9.2, 2.0 Hz, 1H), 7.08 (d, J=8.6 Hz, 1H), 5.86 (dd, J=32.7, 9.6Hz, 1H), 4.64 (p, J=8.9 Hz, 1H); ESIMS m/z 486.9 ([M−H]⁻).

(Z)-4-(3-(3,4-Dichloro-5-(1,1-difluoroethyl)phenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-2-(trifluoromethyl)benzoicacid (C103)

Isolated as a yellow foam (0.05 g, 23%): ¹H NMR (400 MHz, CDCl₃) δ 11.66(s, 1H), 7.85 (dd, J=9.3, 1.8 Hz, 1H), 7.80-7.71 (m, 1H), 7.61 (d, J=2.2Hz, 1H), 7.56 (d, J=8.1 Hz, 1H), 7.26 (s, 1H), 5.86 (dd, J=32.6, 9.6 Hz,1H), 4.86 (p, J=7.0 Hz, 1H), 4.01-3.81 (m, 1H), 2.18-1.93 (m, 3H); ¹⁹FNMR (376 MHz, CDCl₃) δ −57.66, −69.34 (d, J=2.3 Hz), −72.58, −87.48,−106.98; ESIMS m/z 525 ([M−H]⁻).

(Z)-4-(3-(4-Chloro-3-fluoro-5-(trifluoromethyl)phenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-2-(trifluoromethyl)benzoicacid (C104)

Isolated as a yellow gum (1.1 g, 54%): ¹H NMR (400 MHz, CDCl₃) δ 8.03(d, J=8.2 Hz, 1H), 7.98-7.93 (m, 2H), 7.84 (dd, J=8.1, 1.8 Hz, 1H), 7.54(s, 1H), 7.44 (d, J=8.7 Hz, 1H), 5.91 (dd, J=32.4, 9.5 Hz, 1H), 4.72 (p,J=8.8 Hz, 1H); ¹⁹F NMR (376 MHz, CDCl₃) δ −59.64, −62.52, −69.35 (d,J=2.1 Hz), −109.31, −111.51 (d, J=2.3 Hz); ESIMS m/z 512 ([M−H]⁻).

(Z)-4-(3-(3-Bromo-4,5-difluorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-2-(trifluoromethyl)benzoicacid (C105)

Isolated as a yellow gum (1.3 g, 54%): ¹H NMR (400 MHz, CDCl₃) δ 9.76(s, 1H), 8.05 (d, J=8.2 Hz, 1H), 8.01-7.91 (m, 1H), 7.84 (dd, J=8.2, 1.8Hz, 1H), 7.39 (dt, J=4.9, 2.1 Hz, 1H), 7.22 (ddd, J=10.1, 6.6, 2.2 Hz,1H), 5.90 (dd, J=32.5, 9.6 Hz, 1H), 4.62 (q, J=8.9 Hz, 1H); ¹⁹F NMR (376MHz, CDCl₃) δ −59.58, −69.53 (d, J=2.3 Hz), −110.42, −129.11 (d, J=21.5Hz), −132.15 (d, J=21.4 Hz).; ESIMS m/z 505 ([M−H]⁻).

(Z)-4-(3-(3-Chloro-5-(1,1-difluoroethyl)phenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-2-(trifluoromethyl)benzoicacid (C106)

Isolated as a brown foam (0.190 g, 62.1%): ¹H NMR (400 MHz, CDCl₃) δ7.99 (d, J=8.1 Hz, 1H), 7.78 (s, 1H), 7.66 (d, J=8.2 Hz, 1H), 7.52 (s,1H), 7.46 (s, 1H), 7.40 (s, 1H), 6.67 (d, J=15.9 Hz, 1H), 6.56 (dd,J=15.9, 7.7 Hz, 1H), 4.23 (p, J=8.7 Hz, 1H), 1.93 (t, J=18.2 Hz, 3H);¹⁹F NMR (376 MHz, CDCl₃) δ −59.51, −68.50, −88.16 (d, J=9.2 Hz); IR(thin film) 3006, 1706 cm⁻¹; ESIMS m/z 470.9 ([M−H]⁻).

(Z)-4-(3-(3-Chloro-5-(2,2,2-trifluoroethyl)phenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-2-(trifluoromethyl)benzoicacid (C107)

Isolated as an orange oil (0.513 g, 59%); ¹H NMR (400 MHz, CDCl₃) δ 8.03(d, J=8.2 Hz, 1H), 7.96 (s, 1H), 7.83 (dd, J=8.2, 1.3 Hz, 1H), 7.40 (s,1H), 7.33 (s, 1H), 7.22 (s, 1H), 5.93 (dd, J=32.6, 9.7 Hz, 1H), 4.67 (p,J=8.9 Hz, 1H), 3.39 (q, J=10.5 Hz, 2H); ¹⁹F NMR (376 MHz, CDCl₃) δ−59.60, −65.69, −69.25 (d, J=2.3 Hz), −112.97; IR (thin film) 3018, 1710cm⁻¹; ESIMS m/z 507.0 ((M−H]⁻).

(Z)-4-(1,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzoicacid (C108)

Isolated as a brown foam (1.8 g, 49%); ¹H NMR (400 MHz, CDCl₃) δ 8.04(d, J=8.1 Hz, 1H), 7.97 (s, 1H), 7.84 (d, J=8.2 Hz, 1H), 7.42 (s, 2H),6.25-5.80 (m, 2H), 4.55-4.23 (m, 1H); IR (thin film) 2979, 1706, 1615,1573, 1404 cm⁻¹; ESIMS m/z 474.9 ([M−H]⁻).

(Z)-4-(3-(3-Chloro-4-(trifluoromethyl)phenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-2-(trifluoromethyl)benzoicacid (C109)

Isolated as an orange oil (1.22 g, 58%): ¹H NMR (400 MHz, CDCl₃) δ 8.04(d, J=8.2 Hz, 1H), 7.96 (d, J=1.7 Hz, 1H), 7.84 (dd, J=8.3, 1.8 Hz, 1H),7.74 (d, J=8.2 Hz, 1H), 7.57 (d, J=1.6 Hz, 1H), 7.43 (d, J=8.2 Hz, 1H),5.94 (dd, J=32.5, 9.6 Hz, 1H), 4.73 (p, J=8.9 Hz, 1H); IR (thin film)3022, 1710 cm⁻¹; ESIMS m/z 493.0 ([M−H]⁻).

(Z)-4-(3-(3-Chloro-5-(trifluoromethoxy)phenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-2-(trifluoromethyl)benzoicacid (C110)

Isolated as an orange oil (0.744 g, 68%): ¹H NMR (400 MHz, CDCl₃) δ 8.04(d, J=8.2 Hz, 1H), 8.01-7.94 (m, 1H), 7.84 (dd, J=8.2, 1.7 Hz, 1H), 7.36(d, J=1.6 Hz, 1H), 7.27 (dt, J=2.3, 1.1 Hz, 1H), 7.17 (s, 1H), 5.91 (dd,J=32.4, 9.6 Hz, 1H), 4.68 (p, J=8.8 Hz, 1H); ¹⁹F NMR (376 MHz, CDCl₃) δ−57.93, −59.60, −69.24 (d, J=2.5 Hz), −112.31 (d, J=2.6 Hz); IR (thinfilm) 3005, 1712, 1605, 1507, 1408 cm⁻¹; ESIMS m/z 508.8 ([M−H]⁻).

(Z)-4-(3-(3-Chloro-4-(trifluoromethoxy)phenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-2-(trifluoromethyl)benzoicacid (C111)

Isolated as an orange oil (0.428 g, 56%): ¹H NMR (400 MHz, CDCl₃) δ 8.04(d, J=8.2 Hz, 1H), 7.99-7.94 (m, 1H), 7.84 (dd, J=8.2, 1.8 Hz, 1H), 7.54(s, 1H), 7.36 (q, J=1.0 Hz, 2H), 5.93 (dd, J=32.5, 9.7 Hz, 1H), 4.68 (p,J=8.9 Hz, 1H); ¹⁹F NMR (376 MHz, CDCl₃) δ −57.82, −59.60, −69.36 (d,J=2.2 Hz), −112.78 (d, J=2.7 Hz); IR (thin film) 3010, 1711, 1497, 1412cm⁻¹; ESIMS m/z 508.8 ([M−H]⁻).

(Z)-4-(3-(4-Chloro-3-(trifluoromethoxy)phenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-2-(trifluoromethyl)benzoicacid (C112)

Isolated as an orange oil (0.712 g, 65%): ¹H NMR (400 MHz, CDCl₃) δ 8.03(d, J=8.1 Hz, 1H), 7.95 (d, J=1.6 Hz, 1H), 7.83 (dd, J=8.2, 1.8 Hz, 1H),7.53 (d, J=8.3 Hz, 1H), 7.37 (s, 1H), 7.32 (dd, J=8.5, 2.1 Hz, 1H), 5.92(dd, J=32.5, 9.6 Hz, 1H), 4.69 (p, J=8.9 Hz, 1H); ¹⁹F NMR (376 MHz,CDCl₃) δ −57.85, −59.63, −69.49 (d, J=2.2 Hz), −112.48 (t, J=2.7 Hz); IR(thin film) 3089, 1713, 1490 cm⁻¹; ESIMS m/z 508.8 ([M−H]⁻).

(Z)-4-(3-(3-Bromo-4-(trifluoromethyl)phenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-2-(trifluoromethyl)benzoicacid (C113)

Isolated as an orange oil (0.749 g, 65%): ¹H NMR (400 MHz, CDCl₃) δ 8.03(d, J=8.2 Hz, 1H), 7.96 (d, J=1.6 Hz, 1H), 7.86-7.80 (m, 1H), 7.77 (d,J=1.7 Hz, 1H), 7.73 (d, J=8.2 Hz, 1H), 7.51-7.44 (m, 1H), 5.94 (dd,J=32.5, 9.6 Hz, 1H), 4.72 (p, J=8.9 Hz, 1H); ¹⁹F NMR (376 MHz, CDCl₃) δ−59.64 (d, J=21.5 Hz), −62.85, −69.05 (d, J=2.3 Hz), −112.23 (d, J=2.7Hz); IR (thin film) 3084, 1709 cm⁻¹; ESIMS m/z 539.0 ([M−H]⁻).

(Z)-4-(3-(3-chloro-5-hydroxyphenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-2-(trifluoromethyl)benzoicacid (C114)

Isolated as an orange oil (0.090 g, 29.4%): ¹H NMR (400 MHz, CDCl₃) δ8.01 (d, J=8.2 Hz, 1H), 7.95 (t, J=1.2 Hz, 1H), 7.82 (dd, J=8.2, 1.7 Hz,1H), 6.97 (d, J=1.8 Hz, 1H), 6.87 (t, J=2.0 Hz, 1H), 6.80 (d, J=1.8 Hz,1H), 5.90 (dd, J=32.7, 9.8 Hz, 1H), 4.59 (p, J=9.0 Hz, 1H); ¹⁹F NMR (376MHz, CDCl₃) δ −59.60, −69.15 (d, J=2.4 Hz), −113.71 (d, J=3.0 Hz); ESIMSm/z 441.0 ([M−H]⁻).

The following compounds were prepared in like manner to the procedureoutlined in Example 3:

(Z)-4-(3-(3,4-Dichloro-5-vinylphenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-2-(trifluoromethyl)benzoicacid (C115)

Isolated as a yellow wax (0.19 g, 65%): ¹H NMR (400 MHz, CDCl₃) δ 9.76(s, 1H), 8.02 (d, J=8.2 Hz, 1H), 7.95 (s, 1H), 7.82 (d, J=8.2 Hz, 1H),7.52-7.39 (m, 2H), 7.09 (dd, J=17.5, 11.0 Hz, 1H), 6.04-5.85 (m, 1H),5.76 (dd, J=17.5, 13.8 Hz, 1H), 5.55-5.45 (m, 1H), 4.65 (p, J=8.9 Hz,1H); ¹⁹F NMR (376 MHz, CDCl₃) δ −59.56, −67.15, −113.15; ESIMS m/z 487([M−H]⁻).

(Z)-4-(1,4,4,4-Tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-vinylbenzoicacid (C116)

Isolated as a yellow gum (0.3 g, 86%): ¹H NMR (400 MHz, CDCl₃) δ 8.06(d, J=8.4 Hz, 1H), 7.81-7.64 (m, 2H), 7.61-7.49 (m, 2H), 7.44 (s, 2H),5.95-5.67 (m, 2H), 5.47 (dd, J=15.5, 11.0 Hz, 1H), 4.63 (dp, J=13.9, 8.9Hz, 1H); ¹⁹F NMR (376 MHz, CDCl₃) δ −69.35, −112.10; ESIMS m/z 451([M−H]⁻).

(Z)-4-(3-(3-Chloro-5-vinylphenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-2-(trifluoromethyl)benzoicacid (C117)

Isolated as a yellow gum (0.065 g, 58%): ¹H NMR (400 MHz, CDCl₃) δ7.95-7.92 (m, 2H), 7.81 (dd, J=8.2, 1.8 Hz, 1H), 7.57 (dd, J=7.5, 1.7Hz, 1H), 7.41 (t, J=1.8 Hz, 1H), 7.30 (s, 1H), 7.30 (s, 1H), 6.67 (dd,J=17.6, 10.9 Hz, 1H), 5.94 (s, 1H), 5.80 (d, J=17.5 Hz, 1H), 5.37 (d,J=10.9 Hz, 1H), 4.77-4.55 (m, 1H); ¹⁹F NMR (376 MHz, CDCl₃) δ −59.66,−69.30, −112.51; ESIMS m/z 452 ([M−H]⁻).

The following compound was prepared in like manner to the procedureoutlined in Example 7:

(4-(1-Fluorovinyl)-1-naphthoic acid (C118)

Isolated as an off-white solid (0.70 g, 52%): mp 154-156° C.; ¹H NMR(400 MHz, DMSO-d₆) δ 13.40 (br s, 1H), 8.88-8.84 (m, 1H), 8.17-8.10 (m,2H), 7.75-7.66 (m, 3H), 5.39 (dd, J=3.6, 17.2 Hz, 1H), 5.23 (dd, J=36.0,50.4 Hz, 1H); ESIMS m/z 215.20 ([M−H]⁻).

The following compounds were prepared in like manner to the procedureoutlined in Example 8:

5-(1-Bromo-2,2,2-trifluoroethyl)-2-chloro-1-fluoro-3-(trifluoromethyl)benzene(C119)

Isolated as a yellow gum (2.5 g, 49%): ¹H NMR (400 MHz, CDCl₃) δ 7.62(t, J=1.6 Hz, 1H), 7.57 (dd, J=8.7, 2.1 Hz, 1H), 5.12 (q, J=7.0 Hz, 1H);¹⁹F NMR (376 MHz, CDCl₃) δ −62.69, −70.52, −108.76; ESIMS m/z 359([M−H]⁻).

5-(1-Bromo-2,2,2-trifluoroethyl)-1,2-dichloro-3-(1,1-difluoroethyl)benzene (C120)

Isolated as a yellow oil (2 g, 39%): ¹H NMR (400 MHz, CDCl₃) δ 7.91 (dd,J=9.3, 1.8 Hz, 1H), 7.80-7.71 (m, 1H), 5.16 (q, J=7.0 Hz, 1H), 2.22-1.99(m, 3H); ¹⁹F NMR (376 MHz, CDCl₃) δ −59.68, −69.32, −112.07; ESIMS m/z371 ([M−H]⁻).

1-Bromo-5-(1-bromo-2,2,2-trifluoroethyl)-2,3-dichlorobenzene (C121)

Isolated as a yellow oil (4.5 g, 46%): ¹H NMR (400 MHz, CDCl₃) δ 7.58(d, J=2.1 Hz, 1H), 7.46 (d, J=2.1 Hz, 1H), 4.35 (s, 1H); ¹⁹F NMR (376MHz, CDCl₃) δ −70.40; ESIMS m/z 386 ([M−H]⁻).

1-Bromo-5-(1-bromo-2,2,2-trifluoroethyl)-2,3-difluorobenzene (C122)

Isolated as a pale yellow oil (1.8 g, 64%): ¹H NMR (400 MHz, CDCl₃) δ7.52-7.44 (m, 1H), 7.36 (td, J=7.4, 7.0, 3.4 Hz, 1H), 5.03 (q, J=7.0 Hz,1H); ¹⁹F NMR (376 MHz, CDCl₃) δ −70.63, −126.49 (d, J=21.3 Hz), −131.58(dd, J=21.3, 0.9 Hz); ESIMS m/z 336 ([M−H]⁻).

1-(1-Bromo-2,2,2-trifluoroethyl)-3-chloro-5-(1,1-difluoroethyl)benzene(C123)

Isolated as a clear oil (0.665 g, 68%): ¹H NMR (400 MHz, CDCl₃) δ 7.59(s, 1H), 7.53 (s, 1H), 7.50 (s, 1H), 5.10 (q, J=7.2 Hz, 1H), 1.92 (t,J=18.2 Hz, 3H); ¹⁹F NMR (376 MHz, CDCl₃) δ −70.39, −88.36 (d, J=1.6 Hz);IR (thin film) 1588 cm⁻¹; ESIMS m/z 336.4 ([M+H]⁺).

1-(1-Bromo-2,2,2-trifluoroethyl)-3-chloro-5-(2,2,2-trifluoroethyl)benzene(C124)

Isolated as a pale yellow oil (0.930 g, 73%): ¹H NMR (400 MHz, CDCl₃) δ7.51 (s, 1H), 7.35 (s, 1H), 7.32 (s, 1H), 5.07 (q, J=7.2 Hz, 1H), 3.38(q, J=10.5 Hz, 2H); ¹⁹F NMR (376 MHz, CDCl₃) δ −65.71, −70.43; IR (thinfilm) 1113 cm⁻¹; EIMS m/z 356 ([M]⁺).

5-(1-Bromo-2,2-difluoroethyl)-1,2,3-trichlorobenzene (C125)

Isolated as a clear oil (8.3 g, 66.9%): ¹H NMR (400 MHz, CDCl₃) δ 7.49(s, 2H), 6.00 (td, J=55.4, 3.8 Hz, 1H), 4.85 (ddd, J=13.7, 10.4, 3.8 Hz,1H); ¹⁹F NMR (376 MHz, CDCl₃) δ −116.16 (ddd, J=278.0, 55.2, 10.4 Hz),−119.84 (ddd, J=278.1, 55.6, 13.4 Hz); IR (thin film) 1552, 1431 cm⁻¹;ESIMS m/z 323.9 ([M+H]⁺).

4-(1-Bromo-2,2,2-trifluoroethyl)-2-chloro-1-(trifluoromethyl)benzene(C126)

Isolated as a colorless oil (3.33 g, 46%): ¹H NMR (300 MHz, CDCl₃) δ7.73 (d, J=8.2 Hz, 1H), 7.68 (s, 1H), 7.52 (d, J=8.2 Hz, 1H), 5.11 (q,J=7.1 Hz, 1H); ¹³C NMR (75 MHz, CDCl₃) δ 137.94, 133.06 (d, J=1.9 Hz),132.10, 129.93 (q, J=32.0 Hz), 128.10 (q, J=5.3 Hz), 127.47, 124.46 (d,J=48.7 Hz), 120.81 (d, J=43.9 Hz), 44.84 (q, J=34.8 Hz); ESIMS m/z 342.0([M+H]⁺).

1-(1-Bromo-2,2,2-trifluoroethyl)-3-chloro-5-(trifluoromethoxy)benzene(C127)

Isolated as a colorless oil (2.27 g, 60%): ¹H NMR (400 MHz, CDCl₃) δ7.45 (d, J=1.7 Hz, 1H), 7.30 (s, 1H), 7.28 (s, 1H), 5.07 (q, J=7.1 Hz,1H); ¹⁹F NMR (376 MHz, CDCl₃) δ −58.02, −70.44; IR (thin film) 1588,1450 cm⁻¹; EIMS m/z 358 ([M]⁺).

4-(1-Bromo-2,2,2-trifluoroethyl)-2-chloro-1-(trifluoromethoxy)benzene(C128)

Isolated as a colorless oil (2.83 g, 62%): ¹H NMR (400 MHz, CDCl₃) δ7.65 (d, J=2.2 Hz, 1H), 7.45 (dd, J=8.6, 2.3 Hz, 1H), 7.36 (dd, J=8.6,1.5 Hz, 1H), 5.09 (q, J=7.1 Hz, 1H); ¹⁹F NMR (376 MHz, CDCl₃) δ −57.75,−70.52; IR (thin film) 1497 cm⁻¹; EIMS m/z 356 ([M]⁺).

4-(1-Bromo-2,2,2-trifluoroethyl)-1-chloro-2-(trifluoromethoxy)benzene(C129)

Isolated as a clear oil (2.50 g, 56%): ¹H NMR (400 MHz, CDCl₃) δ 7.52(d, J=8.4 Hz, 1H), 7.48 (s, 1H), 7.41 (dd, J=8.4, 2.1 Hz, 1H), 5.10 (q,J=7.1 Hz, 1H); ¹⁹F NMR (376 MHz, CDCl₃) δ −57.94, −70.63; IR (thin film)1492, 1423 cm⁻¹; EIMS m/z 356 ([M]⁺).

2-Bromo-4-(1-bromo-2,2,2-trifluoroethyl)-1-(trifluoromethyl)benzene(C130)

Isolated as a pale yellow oil (3.88 g, 61%): ¹H NMR (400 MHz, CDCl₃) δ7.87 (d, J=1.6 Hz, 1H), 7.74 (d, J=8.2 Hz, 1H), 7.59-7.50 (m, 1H), 5.09(qd, J=6.4, 3.8 Hz, 1H), 2.88 (d, J=4.3 Hz, 1H); ¹⁹F NMR (376 MHz,CDCl₃) δ −62.86, −78.24; IR (thin film) 3392 cm⁻¹; ESIMS m/z 322.0([M−H]⁻).

3-(1-Bromo-2,2,2-trifluoroethyl)-5-chlorophenol (C131)

Isolated as a brown oil (2.29 g, 38%): ¹H NMR (400 MHz, CDCl₃) δ 7.03(d, J=1.7 Hz, 1H), 6.88 (d, J=1.7 Hz, 2H), 6.32 (s, 1H), 4.98 (q, J=7.2Hz, 1H); ¹⁹F NMR (376 MHz, CDCl₃) δ −70.32; ESIMS m/z 288.9 ([M−H]⁻).

1-Bromo-4-(1-bromo-2,2,2-trifluoroethyl)-2-chlorobenzene (C132)

Isolated as a light yellow oil (7.0 g, 51%): ¹H NMR (400 MHz, CDCl₃) δ7.65-7.62 (m, 1H), 7.61-7.59 (m, 1H), 7.29-7.25 (m, 1H), 5.08-5.02 (m,1H); ESIMS m/z 351.9 ([M]⁺).

4-(1-Bromo-2,2,2-trifluoroethyl)-1-chloro-2-methylbenzene (C133)

Isolated as a colorless oil (5.0 g, 44%): ¹H NMR (300 MHz, DMSO-d₆) δ7.55-7.50 (m, 2H), 7.44 (d, J=8.4 Hz, 1H), 6.24-6.16 (m, 1H), 2.36 (s,3H); IR (thin film) 1112, 749, 564 cm⁻¹; ESIMS m/z 286.1 ([M]⁺).

5-(1-Bromo-2,2,2-trifluoroethyl)-1,3-dichloro-2-(difluoromethyl)benzene(C134)

Isolated as a brown solid (2.2 g, 60%): ¹H NMR (400 MHz, DMSO-d₆) δ 7.71(s, 2H), 7.46 (t, J=51.6 Hz, 1H), 6.32-6.26 (m, 1H); ESIMS m/z 335.91([M]⁺).

4-(1-Bromo-2,2,2-trifluoroethyl)-2-chloro-1-methoxybenzene (C135)

Isolated as a pale yellow oil (2.5 g, 33%): ¹H NMR (300 MHz, DMSO-d₆) δ7.61 (s, 1H), 7.55 (d, J=8.7 Hz, 1H), 7.26 (d, J=8.7 Hz, 1H), 6.22-6.14(m, 1H), 3.89 (s, 3H); ESIMS m/z 302.0 ([M]⁺).

4-(1-Bromo-2,2,2-trifluoroethyl)-2-chloro-1-ethylbenzene (C136)

Isolated as a yellow oil (3.5 g, 57%): ¹H NMR (400 MHz, DMSO-d₆) δ 7.59(s, 1H), 7.53-7.45 (m, 2H), 6.25-6.17 (m, 1H), 2.75-2.69 (m, 2H), 1.19(t, J=7.6 Hz, 3H); IR (thin film) 3444, 2926, 1627, 750 cm⁻¹; ESIMS m/z300.00 ([M]⁺).

4-(1-Bromo-2,2,2-trifluoroethyl)-2-chloro-1-(2,2,2-trifluoroethoxy)benzene(C137)

Isolated as a colorless oil (1.50 g, 55%): ¹H NMR (300 MHz, DMSO-d₆) δ7.68 (m, 1H), 7.59-7.55 (m, 1H), 7.38-7.35 (m, 1H), 6.24-6.16 (m, 1H),4.98-4.90 (m, 2H); IR (thin film) 3437, 2929, 1503, 1166 cm⁻¹; ESIMS m/z370.00 ([M]⁺).

5-(1-Bromo-2,2,2-trifluoroethyl)-1-chloro-2,3-difluorobenzene (C138)

Isolated as a colorless oil (2.5 g, 31%): ¹H NMR (400 MHz, CDCl₃) δ7.35-7.28 (m, 2H), 5.05-4.99 (m, 1H); IR (thin film) 2965, 1508, 758cm⁻¹; ESIMS m/z 308.00 ([M]⁺).

1-(1-Bromo-2,2,2-trifluoroethyl)-3-chloro-5-fluorobenzene (C139)

Isolated as a colorless oil (1.3 g, 32%): ¹H NMR (400 MHz, CDCl₃) δ 7.29(s, 1H), 7.17-7.13 (m, 2H), 5.07-5.01 (m, 1H); IR (thin film) 3419,1265, 746 cm⁻¹; ESIMS m/z 290.01 ([M]⁺).

1-Bromo-4-(1-bromo-2,2,2-trifluoroethyl)-2-fluorobenzene (C140)

Isolated as a dark brown oil (0.390 g, 64%): ¹H NMR (300 MHz, CDCl₃) δ7.59 (dd, J=8.3, 7.0 Hz, 1H), 7.31 (dd, J=9.0, 2.2 Hz, 1H), 7.17 (ddt,J=8.2, 2.0, 0.7 Hz, 1H), 5.07 (q, J=7.2 Hz, 1H); IR (thin film) 1684,1257, 1167, 1117 cm⁻¹; ESIMS m/z 336 ([M]⁺).

5-(1-Bromo-2,2,2-trifluoroethyl)-1,2-dichloro-3-methylbenzene (C199)

Isolated as a clear oil (6.7 g, 67%): ¹H NMR (300 MHz, CDCl₃) δ 7.46 (s,1H), 7.28 (s, 1H), 5.02 (q, J=7.2 Hz, 1H), 2.45 (s, 3H); IR (thin film)1260, 1113, 750 cm⁻¹; EIMS m/z 322 ([M]⁺).

The following compounds were prepared in like manner to the procedureoutlined in Example 10:

1-(4-Chloro-3-fluoro-5-(trifluoromethyl)phenyl)-2,2,2-trifluoroethan-1-ol(C141)

Isolated as a yellow gum (5.0 g, 73%): ¹H NMR (400 MHz, CDCl₃) δ 7.63(s, 1H), 7.54 (dd, J=8.9, 1.7 Hz, 1H), 5.16-5.02 (m, 1H), 2.95-2.74 (m,1H); ¹⁹F NMR (376 MHz, CDCl₃) δ −62.56, −78.52, −110.00; ESIMS m/z 296([M−H]⁻).

1-(3,4-Dichloro-5-(1,1-difluoroethyl)phenyl)-2,2,2-trifluoroethan-1-ol(C142)

Isolated as a yellow oil (0.75 g, 87%): ¹H NMR (400 MHz, CDCl₃) δ 7.88(dd, J=9.3, 1.8 Hz, 1H), 7.82-7.69 (m, 1H), 5.04-4.99 (m, 1H), 3.75-3.64(m, 1H), 2.25-2.11 (m, 3H); ¹⁹F NMR (376 MHz, CDCl₃) δ −113.14, −139.92(d, J=20.8 Hz); ESIMS m/z 307 ([M−H]⁻).

1-(3-Bromo-4,5-dichlorophenyl)-2,2,2-trifluoroethan-1-ol (C143)

Isolated as a yellow oil (5.5 g, 86%): ¹H NMR (400 MHz, CDCl₃) δ 7.68(s, 1H), 7.57 (s, 1H), 5.00 (d, J=11.5 Hz, 1H), 4.75 (s, 1H); ¹⁹F NMR(376 MHz, CDCl₃) δ −78.32; ESIMS m/z 323 ([M−H]⁻).

1-(3-Bromo-4,5-difluorophenyl)-2,2,2-trifluoroethan-1-ol (C144)

Isolated as a yellow oil (5.5 g, 90%): ¹H NMR (400 MHz, CDCl₃) δ 7.44(dd, J=17.9, 5.5 Hz, 2H), 5.02 (q, J=6.5 Hz, 1H), 1.55 (br, 1H); ¹⁹F NMR(376 MHz, CDCl₃) δ −78.63, −128.47 (d, J=21.3 Hz), −135.58 (dd, J=21.3,0.9 Hz); ESIMS m/z 291 ([M−H]⁻).

2,2-Difluoro-1-(3,4,5-trichlorophenyl)ethan-1-ol (C145)

Isolated as a pale yellow solid (9.4 g, 98%): ¹H NMR (400 MHz, CDCl₃) δ7.48 (s, 2H), 5.72 (td, J=55.7, 4.7 Hz, 1H), 4.80 (tt, 1=9.3, 4.2 Hz,1H), 2.65 (s, 1H); ¹⁹F NMR (376 MHz, CDCl₃) δ −127.41 (m); IR (thinfilm) 3381 cm⁻¹; ESIMS m/z 260.0 ([M+H]⁺).

1-(3-Chloro-5-fluorophenyl)-2,2,2-trifluoroethan-1-ol (C146)

Isolated as an off-white solid (3.0 g, 83%): ¹H NMR (300 MHz, CDCl₃) δ7.28-7.26 (m, 1H), 7.15-7.12 (m, 2H), 5.04-4.97 (m, 1H), 3.64-3.58 (m,1H); IR (thin film) 3421, 1266, 742 cm⁻¹; ESIMS m/z 228.01 ([M]⁺).

1-(3,4-Dichloro-5-methylphenyl)-2,2,2-trifluoroethan-1-ol (C200)

Isolated as a pale yellow oil (4.6 g, 79%): ¹H NMR (300 MHz, CDCl₃) δ7.44 (s, 1H), 7.26 (s, 1H), 4.97 (q, J=6.6 Hz, 1H), 2.44 (s, 3H); IR(thin film) 3428, 1275, 1262, 750 cm⁻¹; EIMS m/z 258 ([M]⁺).

The following compounds were prepared in like manner to the procedureoutlined in Example 11:

1-(3-Chloro-5-(1,1-difluoroethyl)phenyl)-2,2,2-trifluoroethan-1-ol(C147)

Isolated as a clear oil (0.800 g, 90%): ¹H NMR (400 MHz, CDCl₃) δ 7.56(s, 1H), 7.54 (s, 1H), 7.51 (s, 1H), 5.14-5.01 (m, 1H), 2.77 (s, 1H),1.92 (t, J=18.2 Hz, 3H); ¹⁹F NMR (376 MHz, CDCl₃) δ −78.37, −88.20 (d,J=9.9 Hz); IR (thin film) 3422 cm⁻¹; EIMS m/z 274 ([M]⁺).

1-(3-Chloro-5-(2,2,2-trifluoroethyl)phenyl)-2,2,2-trifluoroethan-1-ol(C148)

Isolated as a pale yellow oil (1.05 g, 61%): ¹H NMR (400 MHz, CDCl₃) δ7.49 (s, 1H), 7.35 (s, 1H), 7.31 (s, 1H), 5.07-5.00 (m, 1H), 3.38 (q,J=10.5 Hz, 2H), 2.64 (d, J=4.4 Hz, 1H); ¹⁹F NMR (376 MHz, CDCl₃) δ−65.75, −78.39; IR (thin film) 3562 cm⁻¹; EIMS m/z 292 ([M]⁺).

1-(3-Chloro-4-(trifluoromethyl)phenyl)-2,2,2-trifluoroethan-1-ol (C149)

Isolated as a colorless oil (5.90 g, 88%): ¹H NMR (400 MHz, CDCl₃) δ7.74 (d, J=8.2 Hz, 1H), 7.68 (s, 1H), 7.50 (d, J=8.1, 2.0, 0.9 Hz, 1H),5.25-4.95 (m, 1H), 3.14 (s, 1H); ¹³C NMR (75 MHz, CDCl₃) δ 139.39,132.66, 130.35, 129.22 (q, J=31.5 Hz), 127.67 (q, J=5.3 Hz),129.69-116.91 (m), 117.16, 71.40 (q, J=32.4 Hz); ESIMS m/z 278.1([M+H]⁺).

1-(3-Chloro-4-(trifluoromethoxy)phenyl)-2,2,2-trifluoroethan-1-ol (C150)

Isolated as a clear oil (3.4 g, 86%): ¹H NMR (400 MHz, CDCl₃) δ 7.64(dq, J=1.9, 0.6 Hz, 1H), 7.47-7.33 (m, 2H), 5.04 (qd, J=6.5, 4.4 Hz,1H), 2.98 (d, J=4.1 Hz, 1H); IR (thin film) 3392, 1496 cm⁻¹; EIMS m/z294 ([M]⁺).

1-(3-Chloro-5-(trifluoromethoxy)phenyl)-2,2,2-trifluoroethan-1-ol (C151)

Isolated as a clear oil (3.15 g, 80%): ¹H NMR (400 MHz, CDCl₃) δ 7.45(s, 1H), 7.30-7.26 (m, 2H), 5.04 (q, J=6.4 Hz, 1H); ¹⁹F NMR (376 MHz,CDCl₃) δ −58.01, −78.40; IR (thin film) 3305, 1587, 1442 cm⁻¹; EIMS m/z294 ([M]⁺).

1-(4-Chloro-3-(trifluoromethoxy)phenyl)-2,2,2-trifluoroethan-1-ol (C152)

Isolated as a clear oil (3.72 g, 95%): ¹H NMR (400 MHz, CDCl₃) δ 7.53(d, J=8.3 Hz, 1H), 7.49 (s, 1H), 7.38 (d, J=8.4 Hz, 1H), 5.06 (dd,J=6.6, 3.4 Hz, 1H), 3.80-3.70 (m, 1H), 2.92 (s, 1H); ¹⁹F NMR (376 MHz,CDCl₃) δ −57.90, −78.59; IR (thin film) 3396, 1489 cm⁻¹; EIMS m/z 294([M]⁺).

1-(3-Bromo-4-(trifluoromethyl)phenyl)-2,2,2-trifluoroethan-1-ol (C153)

Isolated as a pale yellow oil (3.88 g, 61%): ¹H NMR (400 MHz, CDCl₃) δ7.87 (d, J=1.6 Hz, 1H), 7.74 (d, J=8.2 Hz, 1H), 7.59-7.50 (m, 1H), 5.09(qd, J=6.4, 3.8 Hz, 1H), 2.88 (d, J=4.3 Hz, 1H); ¹⁹F NMR (376 MHz,CDCl₃) δ −62.86, −78.24; IR (thin film) 3392 cm⁻¹; ESIMS m/z 322.0([M−H]⁻).

3-Chloro-5-(2,2,2-trifluoro-1-hydroxyethyl)phenol (C154)

Isolated as a yellow solid (5.373 g, 85%): ¹H NMR (400 MHz, CDCl₃) δ6.97 (s, 1H), 6.88 (s, 1H), 6.82 (dq, J=5.1, 2.0 Hz, 1H), 4.95 (qd,J=6.7, 1.6 Hz, 1H); ¹⁹F NMR (376 MHz, CDCl₃) δ −78.28-−82.47 (m); ESIMSm/z 228.1 ([M+H]⁺).

1-(4-Bromo-3-chlorophenyl)-2,2,2-trifluoroethan-1-ol (C155)

Isolated as a brown gum (12 g, 77%): ¹H NMR (400 MHz, CDCl₃) δ 7.65-7.60(m, 1H), 7.59 (s, 1H), 7.23-7.19 (m, 1H), 5.09-5.01 (m, 1H), 2.86 (br s,1H); ESIMS m/z 289.90 ([M]⁺).

1-(4-Chloro-3-methylphenyl)-2,2,2-trifluoroethan-1-ol (C156)

Isolated as a brown oil (7.2 g, 95%): ¹H NMR (300 MHz, DMSO-d₆) δ 7.46(m, 2H), 7.34 (d, J=8.4 Hz, 1H), 5.19-5.10 (m, 1H), 3.62-3.58 (m, 1H),2.34 (s, 3H); IR (thin film) 3400, 1128, 720 cm⁻¹; ESIMS m/z 242.2([M]⁺).

1-(3,5-Dichloro-4-(difluoromethyl)phenyl)-2,2,2-trifluoroethan-1-ol(C157)

Isolated as a pale yellow gum (2.6 g, 62%): ¹H NMR (400 MHz, DMSO-d₆) δ7.73 (s, 2H), 7.45 (t, J=52.0 Hz, 1H), 7.30 (d, J=6.4 Hz, 1H), 5.39 (t,J=6.8 Hz, 1H); IR (thin film) 3418, 1562, 1135 cm⁻¹; ESIMS m/z 293.9([M]⁺).

1-(3-Chloro-4-methoxyphenyl)-2,2, 2-trifluoroethan-1-ol (C158)

Isolated as a brown viscous oil (4.0 g, 79%): ¹H NMR (400 MHz, DMSO-d₆)δ 7.51 (s, 1H), 7.43 (d, J=8.1 Hz, 1H), 7.19 (d, J=8.4 Hz, 1H), 6.85 (d,J=5.2 Hz, 1H), 5.16-5.12 (m, 1H), 3.86 (s, 3H); IR (thin film) 3445,2952, 1606, 1262 cm⁻¹; ESIMS m/z 240.0 ([M]⁺).

1-(3-Chloro-4-ethylphenyl)-2,2,2-trifluoroethan-1-ol (C159)

Isolated as a yellow gum (5.0 g, 36%): ¹H NMR 400 MHz, CDCl₃) δ 7.42 (s,1H), 7.38-7.31 (m, 2H), 5.02-4.95 (m, 1H), 2.81-2.74 (m, 2H), 2.61 (brs, 1H), 1.24 (t, J=8.0 Hz, 3H); IR (thin film) 3420, 2973, 1565, 1131cm⁻¹; ESIMS m/z 238.10 ([M]⁺).

1-(3-Chloro-4-(2,2,2-trifluoroethoxy)phenyl)-2,2,2-trifluoroethan-1-ol(C160)

Isolated as a pale yellow oil (2.0 g, 59%): ¹H NMR (400 MHz, DMSO-d₆) δ7.58 (s, 1H), 7.49-7.44 (m, 1H), 7.33-7.30 (m, 1H), 6.93-6.92 (m, 1H),5.19 (br s, 1H), 4.91-4.86 (m, 2H); IR (thin film) 3428, 2962, 1501,1254 cm⁻¹; ESIMS m/z 308.10 ([M]⁺).

1-(3-Chloro-4,5-difluorophenyl)-2,2,2-trifluoroethan-1-ol (C161)

Isolated as a colorless oil (4.6 g, 33%): ¹H NMR (300 MHz, CDCl₃) δ7.34-7.30 (m, 2H), 5.01-4.95 (m, 1H), 3.21 (br s, 1H); IR (thin film)3302, 1709, 750 cm⁻¹; ESIMS m/z 246.00 ([M]⁺).

The following compound was prepared in like manner to the procedureoutlined in Example 12:

2,2-Difluoro-1-(3,4,5-trichlorophenyl)ethan-1-one (C162)

Isolated as an off-white solid (9.25 g, 88%): mp 45-48° C.; ¹H NMR (400MHz, CDCl₃) δ 7.71 (s, 2H), 6.21 (t, J=53.5 Hz, 1H); ¹⁹F NMR (376 MHz,CDCl₃) δ −126.71 (d, J=53.4 Hz); IR (thin film) 1743, 1559 cm⁻¹; ESIMSm/z 260.0 ([M+H]⁺).

The following compounds were prepared in like manner to the procedureoutlined in Example 13:

N—((R)-1-Oxo-1-((2,2,2-trifluoroethyl)amino)propan-2-yl)-4-((Z)-1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-1-naphthamide(PF1)

Isolated as a yellow solid (0.110 g, 44%).

(Z)-4-(3-(3,4-Dibromophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N-(2-(methyl(2,2,2-trifluoroethyl)amino]-2-oxoethyl)-2-(trifluoromethyl)benzamide(PF4)

Isolated as a yellow gum (0.154 g, 62%).

(Z)-4-(3-(3-Chloro-4-fluorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N-(2-(methyl(2,2,2-trifluoroethyl)amino]-2-oxoethyl)-2-(trifluoromethyl)benzamide(PF6)

Isolated as a yellow gum (0.160 g, 61%).

4-((Z)-3-(3-Chloro-4-fluorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N—((R)-1-oxo-1-((2,2,2-trifluoroethyl)amino)propan-2-yl)-2-(trifluoromethyl)benzamide(PF7)

Isolated as a yellow gum (0.121 g, 43%).

4-((Z)-3-(3-Chloro-4-fluorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N—((R)-1-(methyl(2,2,2-trifluoroethyl)amino)-1-oxopropan-2-yl)-2-(trifluoromethyl)benzamide(PF8)

Isolated as a yellow gum (0.195 g, 74%).

4-((2)-1,4,4,4-Tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-N—((R)-1-thioxo-1-((2,2,2-trifluoroethyl)amino)propan-2-yl)-2-(trifluoromethyl)benzamide(PF96)

Isolated as a yellow oil (0.097 g, 69%).

(Z)-4-(1,4,4,4-Tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-N-(1-((2,2,2-trifluoroethyl)carbamothioyl)cyclopropyl)-2-(trifluoromethyl)benzamide(PF98)

Isolated as a yellow gum (0.047 g, 33%).

4-((Z)-3-(3,5-Dichlorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N—((R)-1-oxo-1-((2,2,2-trifluoroethyl)amino)propan-2-yl)-2-(trifluoromethyl)benzamide(F144)

Isolated as a brown gum (0.100 g, 35%).

(Z)-4-(3-(3-Chloro-4-methoxyphenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)-2-(trifluoromethyl)benzamide(F158)

Isolated as a yellow solid (0.105 g, 42%).

4-((Z)-3-(3-Chloro-4-methoxyphenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N—((R)-1-oxo-1-((2,2,2-trifluoroethyl)amino)propan-2-yl)-2-(trifluoromethyl)benzamide(F161)

Isolated as a yellow solid (0.150 g, 58%).

4-((Z)-3-(3-Chloro-4-ethylphenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N—((R)-1-oxo-1-((2,2,2-trifluoroethyl)amino)propan-2-yl)-2-(trifluoromethyl)benzamide(F164)

Isolated as a yellow gum (0.120 g, 48%).

(Z)-4-(3-(3-Chloro-4-ethylphenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)-2-(trifluoromethyl)benzamide(F165)

Isolated as a pale yellow solid (0.120 g, 51%).

N—((R)-1-Oxo-1-((2,2,2-trifluoroethyl)amino)propan-2-yl)-4-((Z)-1,4,4-trifluoro-3-(3,4,5-trichlorophenyl)hex-1-en-1-yl)-2-(trifluoromethyl)benzamide(F174)

Isolated as a white foamy glass (0.047 g, 60%).

4-((Z)-3-(3-Chloro-5-(1,1-difluoroethyl)phenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N—((R)-1-oxo-1-((2,2,2-trifluoroethyl)amino)propan-2-yl)-2-(trifluoromethyl)benzamide(F175)

Isolated as a pale yellow foam (0.061 g, 55%).

4-((Z)-3-(3-Chloro-5-(2,2,2-trifluoroethyl)phenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N—((R)-1-oxo-1-((2,2,2-trifluoroethyl)amino)propan-2-yl)-2-(trifluoromethyl)benzamide(F176)

Isolated as a white foamy wax (0.079 g, 60.8%).

N—((R)-3-Oxo-2-(2,2,2-trifluoroethyl)isoxazolidin-4-yl)-4-((Z)-1,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide(F177)

Isolated as an off-white solid (0.144 g, 52%).

4-((Z)-3-(3-Chloro-5-(2,2,2-trifluoroethyl)phenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N—((R)-3-oxo-2-(2,2,2-trifluoroethyl)isoxazolidin-4-yl)-2-(trifluoromethyl)benzamide(F178)

Isolated as a white foamy glass (0.052 g, 56%).

4-((Z)-3-(3-Chloro-4-(trifluoromethyl)phenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N—((R)-3-oxo-2-(2,2,2-trifluoroethyl)isoxazolidin-4-yl)-2-(trifluoromethyl)benzamide(F180)

Isolated as a white foam (0.103 g, 74.8%).

4-((Z)-3-(3-Chloro-5-(trifluoromethoxy)phenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N—((R)-1-oxo-1-((2,2,2-trifluoroethyl)amino)propan-2-yl)-2-(trifluoromethyl)benzamide(F181)

Isolated as a clear orange oil (0.077 g, 74.2%).

4-((Z)-3-(3-Chloro-4-(trifluoromethoxy)phenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N—((R)-1-oxo-1-((2,2,2-trifluoroethyl)amino)propan-2-yl)-2-(trifluoromethyl)benzamide(F182)

Isolated as a yellow glass (0.073 g, 89%).

4-((Z)-3-(4-Chloro-3-(trifluoromethoxy)phenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N—((R)-1-oxo-1-((2,2,2-trifluoroethyl)amino)propan-2-yl)-2-(trifluoromethyl)benzamide(F183)

Isolated as a pale yellow glass (0.102 g, 77%).

4-((Z)-3-(3-Bromo-4,5-dichlorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N—((R)-1-oxo-1-((2,2,2-trifluoroethyl)amino)propan-2-yl)-2-(trifluoromethyl)benzamide(F185)

Isolated as a white gum (0.0721 g, 60%).

4-((Z)-3-(3,4-Dichloro-5-(1,1-difluoroethyl)phenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N—((R)-1-oxo-1-((2,2,2-trifluoroethyl)amino)propan-2-yl)-2-(trifluoromethyl)benzamide(F193)

Isolated as a yellow gum (0.044 g, 32%).

4-((Z)-3-(3,4-Dichloro-5-vinylphenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N—((R)-3-oxo-2-(2,2,2-trifluoroethyl)isoxazolidin-4-yl)-2-(trifluoromethyl)benzamide(F196)

Isolated as a colorless gum (0.030 g, 82%).

4-((Z)-3-(3-Bromo-4,5-dichlorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N—((R)-3-oxo-2-(2,2,2-trifluoroethyl)isoxazolidin-4-yl)-2-(trifluoromethyl)benzamide(F197)

Isolated as a white wax (0.091 g, 94%).

2-Bromo-N—((R)-3-oxo-2-(2,2,2-trifluoroethyl)isoxazolidin-4-yl)-4-((Z)-1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzamide(F198)

Isolated as a white wax (0.045 g, 46%).

(Z)—N-(2-Oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)-4-(1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-vinylbenzamide(F200)

Isolated as a yellow gum (0.026 g, 46%).

N—((R)-1-Oxo-1-((2,2,2-trifluoroethyl)amino)propan-2-yl)-4-((Z)-1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl]-2-vinylbenzamide(F201)

Isolated as a colorless gum (0.052 g, 40%).

4-((Z)-3-(4-Chloro-3-fluoro-5-(trifluoromethyl)phenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N—((R)-1-oxo-1-((2,2,2-trifluoroethyl)amino)propan-2-yl)-2-(trifluoromethyl)benzamide(F202)

Isolated as a pale yellow gum (0.052 g, 86%).

(Z)-4-(3-(4-Chloro-3-fluoro-5-(trifluoromethyl)phenyl)-1,4,4,4-tetrafluoro-but-1-en-1-yl)-N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)-2-(trifluoromethyl)benzamide(F203)

Isolated as a yellow oil (0.141 g, 76%).

N—((R)-3-Oxo-2-(2,2,2-trifluoroethyl)isoxazolidin-4-yl)-4-((Z)-1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-vinylbenzamide(F204)

Isolated as a yellow gum (0.101 g, 21%).

4-((Z)-3-(3-Chloro-4-(trifluoromethyl)phenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N—((R)-1-oxo-1-((2,2,2-trifluoroethyl)amino)propan-2-yl)-2-(trifluoromethyl)benzamide(F205)

Isolated as an orange oil (0.081 g, 44.6%).

(Z)-4-(3-(3-Chloro-4-(trifluoromethyl)phenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)-2-(trifluoromethyl)benzamide (F206)

Isolated as an off-white foam (0.074 g, 41%).

4-((Z)-3-(3-Bromo-4,5-difluorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N—((R)-1-oxo-1-((2,2,2-trifluoroethyl)amino)propan-2-yl)-2-(trifluoromethyl)benzamide(F214)

Isolated as an orange oil (0.048 g, 72%).

(Z)-4-(3-(3-Bromo-4,5-difluorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)-2-(trifluoromethyl)benzamide(F217)

Isolated as an orange oil (0.062 g, 81%).

4-((Z)-3-(3-Chloro-5-hydroxyphenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N—((R)-1-oxo-1-((2,2,2-trifluoroethyl)amino)propan-2-yl)-2-(trifluoromethyl)benzamide(C163)

Isolated as an orange oil (0.23 g, 10%): ¹H NMR (400 MHz, CDCl₃) δ 7.86(s, 1H), 7.76 (d, J=8.1 Hz, 1H), 7.56 (d, J=8.1 Hz, 1H), 6.96 (s, 1H),6.85 (t, J=2.1 Hz, 1H), 6.78 (d, J=10.5 Hz, 2H), 6.44 (d, J=7.5 Hz, 1H),5.83 (dd, J=32.8, 9.8 Hz, 1H), 5.63 (s, 1H), 4.74 (p, J=7.1 Hz, 1H),4.56 (p, J=9.0 Hz, 1H), 3.94 (dq, J=9.3, 7.1 Hz, 2H), 1.51 (dd, J=7.0,5.1 Hz, 3H); ¹⁹F NMR (376 MHz, CDCl₃) δ −59.11, −69.19 (d, J=2.6 Hz),−72.56, −113.58; IR (thin film) 3303, 1692, 1531 cm⁻¹; ESIMS m/z 595.3([M+H]⁺).

The following compounds were prepared in like manner to the procedureoutlined in Example 15:

N—((R)-1-(Dimethylamino)-1-oxopropan-2-yl)-4-((Z)-1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide(F172)

Isolated as a white foam (0.134 g, 55%).

N—((R)-1-(Methylamino)-1-oxopropan-2-yl)-4-((Z)-1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide(F173)

Isolated as a white foam (0.0120 g, 51%).

Methyl(Z)-4,4,4-trifluoro-3-(4-(1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamido)butanoate(F166)

Isolated as a yellow/orange gum (0.059 g, 76%).

N—((R)-1-(Hydroxy(2,2,2-trifluoroethyl)amino)-1-oxopropan-2-yl)-4-((Z)-1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide(F169)

Isolated as a white foam (0.117 g, 44%).

4-((Z)-3-(4-Bromo-3-fluorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N—((R)-1-oxo-1-((2,2,2-trifluoroethyl)amino)propan-2-yl)-2-(trifluoromethyl)benzamide(F170)

Isolated as a white foam (0.093 g, 55%).

N—((R)-2-Oxo-1-(2,2,2-trifluoroethyl)pyrrolidin-3-yl)-4-((Z)-1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide(F171)

Isolated as a white foam (0.114 g, 57%).

The following compounds were prepared in like manner to the procedureoutlined in Example 16:

4-((Z)-3-(3,4-Dibromophenyl)-1,4,4,4-tetrafluoro-but-1-en-1-yl)-N—((R)-1-(methyl(2,2,2-trifluoroethyl)amino)-1-oxopropan-2-yl)-2-(trifluoromethyl)benzamide(PF2)

Isolated as a yellow gum (0.169 g, 68%).

(Z)-4-(3-(3,4-Dibromophenyl)-1,4,4,4-tetrafluoro-but-1-en-1-yl)-N-(1-(methyl(2,2,2-trifluoroethyl)carbamoyl)cyclopropyl)-2-(trifluoromethyl)benzamide(PF3)

Isolated as a yellow solid (0.157 g, 60%).

(Z)-4-(3-(3-Chloro-4-fluorophenyl)-1,4,4,4-tetrafluoro-but-1-en-1-yl)]-N-(1-(methyl(2,2,2-trifluoroethyl)carbamoyl)cyclopropyl)-2-(trifluoromethyl)benzamide(PF10)

Isolated as a brown gum (0.142 g, 53%).

(Z)-4-(3-(3,4-Dichloro-5-methylphenyl)-1,4,4,4-tetrafluoro-but-1-en-1-yl)-N-(2-(methyl(2,2,2-trifluoroethyl)amino)-2-oxoethyl)-2-(trifluoromethyl)benzamide(PF12)

Isolated as a pale yellow solid (0.176 g, 57%).

4-((Z)-3-(3,4-Dichloro-5-methylphenyl)-1,4,4,4-tetrafluoro-but-1-en-1-yl)-N—((R)-1-oxo-1-(2,2,2-trifluoroethyl)amino)propan-2-yl)-2-(trifluoromethyl)benzamide(PF13)

Isolated as a pale yellow solid (0.155 g, 54%).

4-((Z)-3-(3,4-Dichloro-5-methylphenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N—((R)-1-(methyl(2,2,2-trifluoroethyl)amino)-1-oxopropan-2-yl)-2-(trifluoromethyl)benzamide(PF14)

Isolated as a yellow gum (0.165 g, 60%).

(Z)-4-(3-(3,4-Dichloro-5-methylphenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N-(1-(2,2,2-trifluoroethyl)carbamoyl)cyclopropyl)-2-(trifluoromethyl)benzamide(PF15)

Isolated as a pale yellow solid (0.140 g, 51%).

(Z)-4-(3-(3,4-Dichloro-5-methylphenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N-(1-(methyl(2,2,2-trifluoroethyl)carbamoyl)cyclopropyl)-2-(trifluoromethyl)benzamide(PF16)

Isolated as a yellow solid (0.175 g, 64%).

(Z)-4-(3-(4-Chloro-3-fluorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N-(2-(methyl(2,2,2-trifluoroethyl)amino)-2-oxoethyl)-2-(trifluoromethyl)benzamide(PF18)

Isolated as a white solid (0.153 g, 48%).

4-((Z)-3-(4-Chloro-3-fluorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N—((R)-1-oxo-1-((2,2,2-trifluoroethyl)amino)propan-2-yl)-2-(trifluoromethyl)benzamide(PF19)

Isolated as a yellow solid (0.088 g, 41%).

4-((Z)-3-(4-Chloro-3-fluorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N—((R)-1-(methyl(2,2,2-trifluoroethyl)amino)-1-oxopropan-2-yl)-2-(trifluoromethyl)benzamide(PF20)

Isolated as a yellow gum (0.150 g, 47%).

(Z)-4-(3-(4-Chloro-3-fluorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N-(1-(methyl(2,2,2-trifluoroethyl)carbamoyl)cyclopropyl)-2-(trifluoromethyl)benzamide(PF22)

Isolated as a yellow gum (0.090 g, 33%).

(Z)-4-(3-(4-Bromo-3-chlorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N-(2-(methyl(2,2,2-trifluoroethyl)amino)-2-oxoethyl)-2-(trifluoromethyl)benzamide(PF24)

Isolated as a yellow gum (0.101 g, 43%).

4-((Z)-3-(4-Bromo-3-chlorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N—((R)-1-oxo-1-(2,2,2-trifluoroethyl)amino)propan-2-yl)-2-(trifluoromethyl)benzamide(PF25)

Isolated as a pale brown solid (0.168 g, 65%).

4-((Z)-3-(4-Bromo-3-chlorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl]-N—((R)-1-(methyl(2,2,2-trifluoroethyl)amino)-1-oxopropan-2-yl)-2-(trifluoromethyl)benzamide(PF26)

Isolated as a pale yellow solid (0.076 g, 32%).

(Z)-4-(3-(4-Bromo-3-chlorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N-(1-(2,2,2-trifluoroethyl)carbamoyl)cyclopropyl)-2-(trifluoromethyl)benzamide(PF27)

Isolated as an off-white solid (0.149 g, 57%).

(Z)-4-(3-(4-Bromo-3-chlorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl]-N-(1-(methyl(2,2,2-trifluoroethyl)carbamoyl)cyclopropyl)-2-(trifluoromethyl)benzamide(PF28)

Isolated as an off-white solid (0.055 g, 23%).

4-((Z)-3-(3-Bromo-5-chlorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N—((R)-1-(methyl(2,2,2-trifluoroethyl)amino)-1-oxopropan-2-yl)-2-(trifluoromethyl)benzamide(PF31)

Isolated as a yellow gum (0.124 g, 54%).

(Z)-4-(3-(3-Bromo-5-chlorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N-(1-((2,2,2-trifluoroethyl)carbamoyl)cyclopropyl)-2-(trifluoromethyl)benzamide(PF32)

Isolated as a brown gum (0.115 g, 56%).

(Z)-4-(3-(3-Bromo-5-chlorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N-(1-(methyl(2,2,2-trifluoroethyl)carbamoyl)cyclopropyl)-2-(trifluoromethyl)benzamide(PF33)

Isolated as a yellow gum (0.136 g, 51%).

(Z)-4-(3-(3-Bromo-4-chlorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N-(2-(methyl(2,2,2-trifluoroethyl)amino)-2-oxoethyl)-2-(trifluoromethyl)benzamide(PF35)

Isolated as a yellow gum (0.111 g, 56%).

4-((Z)-3-(3-Bromo-4-chlorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N—((R)-1-(methyl(2,2,2-trifluoroethyl)amino)-1-oxopropan-2-yl)-2-(trifluoromethyl)benzamide(PF37)

Isolated as a yellow gum (0.131 g, 67%).

(Z)-4-(3-(3-Bromo-4-chlorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N-(1-(methyl(2,2,2-trifluoroethyl)carbamoyl)cyclopropyl)-2-(trifluoromethyl)benzamide(PF39)

Isolated as a yellow gum (0.107 g, 47%).

(Z)-4-(3-(3-Chloro-5-(trifluoromethyl)phenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N-(2-(methyl(2,2,2-trifluoroethyl)amino)-2-oxoethyl)-2-(trifluoromethyl)benzamide(PF41)

Isolated as a pale yellow solid (0.077 g, 32%).

4-((Z)-3-(3-Chloro-5-(trifluoromethyl)phenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N-((1R)-1-oxo-1-((2,2,2-trifluoroethyl)amino)propan-2-yl)-2-(trifluoromethyl)benzamide(PF42)

Isolated as a yellow solid (0.076 g, 32%).

4-((Z)-3-(3-Chloro-5-(trifluoromethyl)phenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N—((R)-1-(methyl(2,2,2-trifluoroethyl)amino)-1-oxopropan-2-yl)-2-(trifluoromethyl)benzamide(PF43)

Isolated as a brown gum (0.051 g, 21%).

(Z)-4-(3-(3-Chloro-5-(trifluoromethyl)phenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)]-N-(1-((2,2,2-trifluoroethyl)carbamoyl)cyclopropyl)-2-(trifluoromethyl)benzamide(PF44)

Isolated as a pale brown solid (0.088 g, 37%).

(Z)-4-(3-(3-Chloro-5-(trifluoromethyl)phenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N-(1-(methyl(2,2,2-trifluoroethyl)carbamoyl)cyclopropyl)-2-(trifluoromethyl)benzamide(PF45)

Isolated as a brown solid (0.045 g, 18%).

(Z)-4-(3-(4-Chloro-3-methylphenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N-(2-(methyl(2,2,2-trifluoroethyl)amino]-2-oxoethyl)-2-(trifluoromethyl)benzamide (PF47)

Isolated as a pale yellow solid (0.100 g, 41%).

4-((Z)-3-(4-Chloro-3-methylphenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N—((R)-1-oxo-1-(2,2,2-trifluoroethyl)amino)propan-2-yl)-2-(trifluoromethyl)benzamide(PF48)

Isolated as a pale yellow solid (0.080 g, 33%).

4-((Z)-3-(4-Chloro-3-methylphenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N—((R)-1-(methyl(2,2,2-trifluoroethyl)amino)-1-oxopropan-2-yl)-2-(trifluoromethyl)benzamide(PF49)

Isolated as an off-white solid (0.058 g, 28%).

(Z)-4-(3-(4-Chloro-3-methylphenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N-(1-((2,2,2-trifluoroethyl)carbamoyl)cyclopropyl)-2-(trifluoromethyl)benzamide(PF50)

Isolated as a pale yellow solid (0.106 g, 39%).

(Z)-4-(3-(4-Chloro-3-methylphenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N-(1-(methyl(2,2,2-trifluoroethyl)carbamoyl)cyclopropyl)-2-(trifluoromethyl)benzamide(PF51)

Isolated as a pale yellow solid (0.098 g, 39%).

2-Chloro-N—((R)-1-oxo-1-((2,2,2-trifluoroethyl)amino)propan-2-yl)-4-((Z)-1,4,4-trifluoro-3-(3,4,5-trichlorophenyl)pent-1-en-1-yl)benzamide(PF60)

Isolated as a pale brown solid (0.100 g, 32%).

(Z)-2-Chloro-4-(1,4,4-trifluoro-3-(3,4,5-trichlorophenyl)pent-1-en-1-yl)-N-(1-((2,2,2-trifluoroethyl)carbamoyl)cyclopropyl)benzamide(PF62)

Isolated as a pale yellow gum (0.101 g, 33%).

N—((R)-1-Oxo-1-((2,2,2-trifluoroethyl)amino)propan-2-yl)-4-((Z)-1,4,4,4-tetrafluoro-3-(4-fluoro-3-(trifluoromethyl)phenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide(F141)

Isolated as a pale yellow solid (0.190 g, 51%).

4-((Z)-3-(3,5-Dichloro-4-(difluoromethyl)phenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N—((R)-1-oxo-1-((2,2,2-trifluoroethyl)amino)propan-2-yl)-2-(trifluoromethyl)benzamide(F142)

Isolated as a pale yellow solid (0.130 g, 50%).

4-((2)-3-(3,5-Dichloro-4-(difluoromethyl)phenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N—((R)-3-oxo-2-(2,2,2-trifluoroethyl)isoxazolidin-4-yl)-2-(trifluoromethyl)benzamide(F143)

Isolated as a pale yellow gum (0.112 g, 52%).

(Z)-4-(3-(4-Bromo-3,5-dichlorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N-(1-(methyl(2,2,2-trifluoroethyl)carbamoyl)cyclopropyl)-2-(trifluoromethyl)benzamide(F145)

Isolated as a yellow gum (0.085 g, 37%).

N—((R)-3-Oxo-2-(2,2,2-trifluoroethyl)isoxazolidin-4-yl)-4-((2)-1,4,4,4-tetrafluoro-3-(4-fluoro-3-(trifluoromethyl)phenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide(F150)

Isolated as a brown gum (0.100 g, 37%).

(Z)-4-(3-(3-Chloro-4,5-difluorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)-2-(trifluoromethyl)benzamide(F153)

Isolated as a brown gum (0.110 g, 47%).

4-((Z)-3-(3-Chloro-4,5-difluorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N—((R)-1-oxo-1-((2,2,2-trifluoroethyl)amino)propan-2-yl)-2-(trifluoromethyl)benzamide(F154)

Isolated as a pale yellow gum (0.119 g, 50%).

N—((R)-3-Oxo-2-(2,2,2-trifluoroethyl)isoxazolidin-4-yl)-4-((Z)-1,4,4,4-tetrafluoro-3-(3,4,5-trifluorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide(F155)

Isolated as a pale yellow gum (0.110 g, 56%).

(Z)-4-(3-(3-Chloro-5-fluorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)-2-(trifluoromethyl)benzamide(F157)

Isolated as a pale yellow gum (0.085 g, 51%).

N—((R)-1-Oxo-1-((2,2,2-trifluoroethyl)amino)propan-2-yl)-4-((Z)-1,4,4,4-tetrafluoro-3-(3,4,5-trifluorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide(F159)

Isolated as a pale yellow gum (0.120 g, 44%).

(Z)—N-(2-Oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)-4-(1,4,4,4-tetrafluoro-3-(3,4,5-trifluorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide(F160)

Isolated as an off-white solid (0.115 g, 41%).

4-((Z)-3-(3-Chloro-4-(2,2,2-trifluoroethoxy)phenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N—((R)-1-oxo-1-((2,2,2-trifluoroethyl)amino)propan-2-yl)-2-(trifluoromethyl)benzamide(F162)

Isolated as a yellow gum (0.115 g, 44%).

(Z)—N-(2-Oxo-2-((2-oxopropyl)amino)ethyl)-4-(1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide(F163)

Isolated as a pale brown gum (0.112 g, 49%).

The following compounds were prepared in like manner to the procedureoutlined in Example 21:

2-Amino-N-(2-hydroxy-2-methylpropyl)acetamide hydrochloride (C164)

Isolated as a colorless gum (0.45 g, 31%): ¹H NMR (400 MHz, DMSO-d₆) δ8.56 (br s, 2H), 8.16 (br s, 3H), 3.61-3.15 (m, 2H), 3.09-3.07 (m, 2H),1.53 (s, 3H), 1.07 (s, 3H); ESIMS m/z 147.35 ([M+H]⁺).

(R)-2-Amino-N′-(2,2,2-trifluoroethyl)propanehydrazide hydrochloride(C165)

Isolated as an off-white solid (0.15 g, 68%): ¹H NMR (400 MHz, DMSO-d₆)δ 10.06 (s, 1H), 8.30 (br s, 3H), 3.76-3.72 (m, 1H), 3.56 (s, 1H),3.48-3.38 (m, 2H), 1.34 (d, J=6.8 Hz, 3H); IR (thin film) 3425, 1683,1145 cm⁻¹; ESIMS m/z 186.30 ([M+H]⁺).

(R)-2-Amino-N-methyl-N′-(2,2,2-trifluoroethyl)propanehydrazidehydrochloride (C166)

Isolated as a pale yellow solid (0.50 g, 91%): ¹H NMR (300 MHz, DMSO-d₆)δ 8.26 (br s, 3H), 6.08 (br s, 1H), 4.36-4.28 (m, 1H), 3.68-3.64 (m,2H), 3.03 (s, 3H), 1.34 (d, J=6.9 Hz, 3H); IR (thin film) 3452, 1667,764 cm⁻¹; ESIMS m/z 200.30 ([M+H]⁺).

1-Methyl-2-(2,2,2-trifluoroethyl)hydrazine hydrochloride (C167)

Isolated as an off white solid (0.70 g, 97%): ¹H NMR (300 MHz, DMSO-d₆)δ 10.82 (br s, 2H), 6.68 (br s, 1H), 3.90-3.74 (m, 2H), 2.66 (s, 3H);ESIMS m/z 129.10 ([M+H]⁺).

(R)-2-Amino-N,N′-dimethyl-N′-(2,2,2-trifluoroethyl)propanehydrazidehydrochloride (C168)

Isolated as an off-white solid (0.30 g, 75%): ¹H NMR (300 MHz, DMSO-d₆)δ 8.17 (br s, 3H), 4.14-4.07 (m, 1H), 3.71-3.56 (m, 2H), 2.92 (s, 3H),2.69 (s, 3H), 1.36 (d, J=7.2 Hz, 3H); ESIMS m/z 214.00 ([M+H]⁺).

1,2-Dimethyl-1-(2,2,2-trifluoroethyl)hydrazine hydrochloride (C169)

Isolated as an off-white solid (0.50 g, 68%): ¹H NMR (300 MHz, DMSO-d₆)δ 10.90 (s, 2H), 3.86-3.77 (m, 2H), 2.78 (s, 3H), 2.59 (m, 3H); IR (thinfilm) 2464, 1634, 790 cm⁻¹.

2-Amino-N-(2-oxopropyl)acetamide hydrochloride (C170)

Isolated as a brown gum (0.40 g, 60%): ¹H NMR (400 MHz, DMSO-d₆) δ 8.72(br s, 1H), 8.20 (br s, 3H), 4.05-4.03 (m, 2H), 3.61-3.60 (m, 2H), 2.10(s, 3H); IR (thin film) 3421, 1261 cm⁻¹.

2-Amino-N-ethyl-N-(2,2,2-trifluoroethyl)acetamide hydrochloride (C171)

Isolated as a pink solid (2.33 g, 93%): mp 158-162° C.: ¹H NMR (400 MHz,DMSO-d₆) δ 8.30 (s, 3H), minor rotamer 4.35 (q, J=9.2 Hz, 2H), majorrotamer 4.23 (q, J=9.5 Hz, 2H), minor rotamer 3.98 (s, 2H), 3.43 (d,1=7.0 Hz, 2H), 2.53 (m, 2H), minor rotamer 1.17 (m, 3H), minor rotamer1.09 (m, 3H); ¹⁹F NMR (376 MHz, DMSO-d₆) δ major rotamer −68.20, minorrotamer −69.03; IR (thin film) 1665, 1156, 1109 cm⁻¹.

(R)-2-Amino-N-(3,3-difluorocyclobutyl)propanamide hydrochloride (C172)

Isolated and carried on without further purification as a brown viscousoil: ¹⁹F NMR (376 MHz, Methanol-d₄) δ −85.81 (d, J=199.0 Hz), −99.35 (d,J=199.1 Hz); IR (thin film) 1669, 1299 cm⁻¹.

The following compound was prepared in like manner to the procedureoutlined in Example 22:

tert-Butyl(R)-(1-((3,3-difluorocyclobutyl)amino)-1-oxopropan-2-yl)carbamate (C173)

Isolated as a white solid (1.57 g, 51%): mp 149-153° C.; ¹H NMR (400MHz, CDCl₃) 6.75 (br s, 1H), 4.96 (br s, 1H), 4.30-4.19 (m, 1H),4.18-4.07 (m, 1H), 3.04-2.94 (m, 2H), 2.54-2.39 (m, 2H), 1.45 (s, 9H),1.34 (d, J=7.1 Hz, 3H); ¹⁹F NMR (376 MHz, Methanol-d₄) δ −84.89 (d,J=198.9 Hz), −97.22 (d, J=199.1 Hz); IR (thin film) 1680, 1652, 1522,1157 cm⁻¹; ESIMS m/z 222 ([M-C₄H₉]⁺).

The following compound was prepared in like manner to the procedureoutlined in Example 30:

Benzyl(R)-(1-((benzyloxy)(2,2,2-trifluoroethyl)amino)-1-oxopropan-2-yl)carbamate(C174)

Isolated as a colorless oil (0.350 g, 40%): ¹H NMR (300 MHz, CDCl₃) δ7.39 (m, 10H), 5.42 (d, J=8.6 Hz, 1H), 5.14 (m, 2H), 5.03 (s, 2H), 4.87(m, 1H), 4.56 (m, 1H), 3.82 (dd, J=15.9, 8.0 Hz, 1H), 1.36 (d, J=7.0 Hz,3H); IR (thin film) 1684, 1256, 1188, 1154, 696 cm⁻¹; ESIMS m/z 411.2([M+H]⁺).

The following compound was prepared in like manner to the procedureoutlined in Example 31:

(R)-2-Amino-N-hydroxy-N-(2,2,2-trifluoroethyl)propanamide hydrochloride(C175)

Isolated and carried on without further purification as a brown viscousoil: ¹H NMR (300 MHz, DMSO-d₆) δ 11.14 (s, 1H), 8.37 (s, 3H), 4.62-4.27(m, 2H), 3.49-3.38 (m, 1H), 1.43 (d, J=6.9 Hz, 3H); ESIMS m/z 184.9([M−H]⁻).

The following compound was prepared in like manner to the procedureoutlined in Example 34:

(R)-3-Amino-1-(2,2,2-trifluoroethyl)pyrrolidin-2-one hydrochloride(C176)

Isolated as a white solid (0.320 g, 59%): ¹H NMR (300 MHz, DMSO-d₆) δ8.55 (s, 3H), 4.16 (dddd, J=24.0, 14.3, 9.7, 5.1 Hz, 3H), 3.55-3.47 (m,2H), 2.42 (ddd, J=13.0, 6.5, 3.4 Hz, 1H), 1.99 (dq, J=12.5, 9.5 Hz, 1H).

Example 35: Preparation of(Z)-(4-(1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)phenylcarbonothioyl)glycine(C177)

To tert-butyl(Z)-(4-(1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)phenylcarbonothioyl)glycinate(C178) (0.236 g, 0.378 mmol) in dichloromethane (5 mL) was addedtrifluoroacetic acid (0.116 mL, 1.51 mmol). After stirring 20 hours atroom temperature and 1 hour at reflux, the mixture was cooled to roomtemperature and additional trifluoroacetic acid (0.233 mL, 3.02 mmol)was added. After 30 minutes the mixture was concentrated under reducedpressure. Purification of the residue by column chromatography (SiO₂,eluting with 0-100% ethyl acetate gradient in hexanes) afforded thetitle compound as a yellow foam (0.066 g, 29%): ¹H NMR (400 MHz, CDCl₃)δ 9.06 (s, 1H), 7.84 (s, 1H), 7.82 (d, J=1.7 Hz, 1H), 7.74 (dd, J=8.3,1.7 Hz, 1H), 7.63 (d, J=8.1 Hz, 1H), 7.43 (s, 2H), 5.81 (dd, J=32.6, 9.6Hz, 1H), 4.65-4.56 (m, 3H); ¹⁹F NMR (376 MHz, CDCl₃) δ −58.34, −69.35,−111.88; ESIMS m/z 567 [(M−H)⁻].

Example 36: Preparation of tert-butyl(Z)-(4-(1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)phenylcarbonothioyl)glycinate(C178)

A 5 mL microwave reaction vial was charged with2,4-bis(4-methoxyphenyl)-1,3,2,4-dithiadiphosphetane 2,4-disulfide(0.150 g, 0.369 mmol), tert-butyl(Z)-(4-(1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)phenylcarbonothioyl)glycinate(C178) (0.300 g, 0.493 mmol) and dioxane (2.0 mL). The mixture, under anitrogen atmosphere, was placed in a microwave reactor and heated to 60°C. for 10 hours and 90° C. for 6 hours. After cooling the mixture wasthen treated with additional4-bis(4-methoxyphenyl)-1,3,2,4-dithiadiphosphetane 2,4-disulfide (0.125g, 0.309 mmol), placed in a microwave reactor and heated to 95° C. for 4hours. After cooling, the crude mixture was diluted with ethyl acetateand diethyl ether, then washed with saturated sodium bicarbonate andbrine. The organic phase was dried with sodium sulfate, concentrated,and purified by column chromatography (SiO₂, eluting with a 0-100%gradient of ethyl acetate in hexanes) to afford the title compound as ayellow glass (0.230 g, 67%): ¹H NMR (400 MHz, CDCl₃) δ 7.95 (d, J=4.5Hz, 1H), 7.81 (d, J=1.7 Hz, 1H), 7.73 (dd, J=8.2, 1.7 Hz, 1H), 7.62 (d,J=8.2 Hz, 1H), 7.44 (s, 2H), 5.80 (dd, J=32.6, 9.6 Hz, 1H), 4.61 (p,J=8.9 Hz, 1H), 4.40 (d, J=4.4 Hz, 2H), 1.51 (s, 9H); ¹⁹F NMR (376 MHz,CDCl₃) δ −58.37, −69.37, −111.87; ESIMS m/z 623 ([M−H]⁻).

Example 37: Preparation of 4-vinyl-1-naphthoic acid (C179)

To a stirred solution of 4-bromo-1-naphthoic acid (2.50 g, 9.98 mmol) indimethyl sulfoxide (32.3 mL) was added potassium vinyltrifluoroborate(1.33 g, 9.96 mmol), potassium carbonate (3.85 g, 27.9 mmol) and[1,1′-bis(diphenylphosphino)ferrocene]-dichloropalladium(II) (0.364 g,0.498 mmol). The reaction mixture was heated in an 80° C. bath for 18hours. The reaction mixture was cooled to ambient temperature anddiluted with 1 N aqueous hydrochloric acid solution (150 mL) and water(150 mL). The mixture was extracted with ethyl acetate. The organiclayer was washed with brine, dried over sodium sulfate and concentratedunder reduced pressure to afford crude compound. The crude compound waspurified by column chromatography (SiO₂, eluting with 0-100% ethylacetate gradient in hexanes) to afford the title compound as a brightyellow solid (1.36 g, 62%): mp 147-155° C.; ¹H NMR (300 MHz, acetone-d₆)δ 11.42 (s, 1H), 9.16-9.03 (m, 1H), 8.31-8.25 (m, 2H), 7.77 (dd, J=7.7,0.7 Hz, 1H), 7.70-7.57 (m, 3H), 5.95 (dd, J=17.2, 1.5 Hz, 1H), 5.62 (dd,J=11.1, 1.5 Hz, 1H); ESIMS m/z 197.1 ([M−H]⁻).

Example 38: Preparation of1-(4-Bromo-3-fluorophenyl)-2,2,2-trifluoroethan-1-ol (C180)

To a stirred solution of lithium acetate (0.016 g, 0.25 mmol) indimethylformamide (2 mL) cooled in an ice bath were added4-bromo-3-fluorobenzaldehyde (1.00 g, 4.93 mmol) andtrimethyl(trifluoromethyl)silane (0.841 g, 5.91 mmol). The mixture wasallowed to warm to room temperature. After 18 hours the mixture wasportioned between diethyl ether and saturated aqueous ammonium chloride.The organic layer was washed brine (2×), dried over sodium sulfate andconcentrated to afford a light brown oil. The crude intermediate wastaken up in tetrahydrofuran (20 mL) and treated with 1N aqueoushydrochloric acid solution (5 mL). After stirring for 18 hours at roomtemperature the reaction mixture was concentrated and the residuepartitioned between diethyl ether and aqueous saturated sodiumbicarbonate. The organic layer was dried over magnesium sulfate andconcentrated under reduced pressure to afford crude compound.Purification by column chromatography (SiO₂, eluting with 10% ethylacetate in hexanes) afforded the title compound as a pale oil (0.800 g,60%): ¹H NMR (400 MHz, CDCl₃) δ 7.60 (dd, J=8.3, 6.9 Hz, 1H), 7.30 (dd,J=9.1, 2.0 Hz, 1H), 7.15 (dq, J=8.3, 0.8 Hz, 1H), 5.02 (dd, J=6.5, 4.5Hz, 1H), 2.65 (d, J=4.4 Hz, 1H).

Example 39: Preparation 1-Bromo-3-chloro-5-(2,2,2-trifluoroethyl)benzene(C181)

(3-Bromo-5-chlorophenyl)boronic acid (4 g, 17.00 mmol) was added to aflask with 2,2,2-trifluoroethan-1-amine hydrochloride (9.22 g, 68.0mmol), sodium nitrite (5.87 g, 85 mmol), and ammonium chloride (3.64 g,68.0 mmol). The reaction was heated to 100° C. overnight. At this point,the solvent was removed, and the residue was dissolved in dimethylsulfoxide (20 mL). Potassium fluoride (1.976 g, 34.0 mmol) was added,and the mixture was heated to 100° C. for 2 hours. After cooling, themixture was diluted with water and extracted with dichloromethane. Afterextraction and solvent removal, the residue was purified by silica gelchromatography eluting with hexanes. The title compound was recovered asa clear, colorless oil that crystallized upon standing (3.00 g, 64.5%):¹H NMR (400 MHz, CDCl₃) δ 7.52 (t, J=1.8 Hz, 1H), 7.35 (s, 1H), 7.24 (s,1H), 3.32 (q, J=10.5 Hz, 2H); ¹⁹F NMR (376 MHz, CDCl₃) 5-65.64; ESIMSm/z 274.0 ([M+H]⁺).

Example 40: Preparation of 3-chloro-5-(2,2,2-trifluoroethyl)benzaldehyde(C182)

1-Bromo-3-chloro-5-(2,2,2-trifluoroethyl)benzene (C181) (2 g, 7.31 mmol)was dissolved in tetrahydrofuran at 0° C., and isopropylmagnesiumchloride-lithium chloride complex (1.3 M solution in tetrahydrofuran;6.75 mL, 8.78 mmol) was added dropwise. The reaction mixture was stirredfor 4 hours with warming to room temperature, and N,N-dimethylformamide(0.680 mL, 8.78 mmol) was added dropwise. The reaction mixture wasstirred for 30 minutes, then 1 N aqueous hydrochloric acid was added,and the mixture was extracted with diethyl ether. The combined organiclayers were washed with brine, dried over sodium sulfate andconcentrated to a yellow oil. Purification by silica gel chromatographyeluting 0-20% acetone in hexanes gave the title compound as a paleyellow oil (1.33 g, 82%): ¹H NMR (400 MHz, CDCl₃) δ 9.98 (s, 1H),7.90-7.78 (m, 1H), 7.71 (s, 1H), 7.56 (s, 1H), 3.45 (q, J=10.5 Hz, 2H);¹⁹F NMR (376 MHz, CDCl₃) δ −65.67; IR (thin film) 1704 cm⁻¹; EIMS m/z221 ([M]⁺).

Example 41: Preparation of 3,5-dichloro-4-(difluoromethyl)benzaldehyde(C183)

To a stirred solution of methyl 3,5-dichloro-4-(difluoromethyl)benzoate(C189) (5.00 g, 19.6 mmol) in methylene chloride (20 mL) cooled in a−78° C. bath was added dropwise diisobutylaluminum hydride (1 M solutionin tetrahydrofuran; 39.2 mL, 39.2 mmol). After 2 hours, the reactionmixture was treated with cold water and extracted with methylenechloride. The organic layer was washed with brine, dried over sodiumsulfate, and concentrated under reduced pressure to afford crudecompound. Purification by column chromatography (SiO₂, 100-200 mesh,eluting with 5% ethyl acetate in petroleum ether) afforded the titlecompound as a pale brown solid (3.0 g, 66%): ¹H NMR (400 MHz, DMSO-d₆) δ10.00 (s, 1H), 8.05 (s, 2H), 7.52 (t, J=52.0 Hz, 1H); IR (thin film)1709, 1362, 1057 cm⁻¹; ESIMS m/z 224.0 ([M]⁺).

Example 42: Preparation of 3-chloro-4,5-difluorobenzaldehyde (C184)

To a stirred solution of methyl(3-chloro-4,5-difluorophenyl)methanol(4.00 g, 22.4 mmol) in methylene chloride (150 mL) was added manganesedioxide (15.0 g, 179 mmol). After stirring for 12 hours at roomtemperature, the reaction mixture was filtered through Celite®. Thefiltrate was concentrated under reduced pressure to afford the titlecompound as a colorless oil (3.5 g, 86%): ¹H NMR (300 MHz, CDCl₃) δ 9.89(s, 1H), 7.77-7.74 (m, 1H), 7.66-7.61 (m, 1H); IR (thin film) 3302,1709, 750 cm⁻¹; ESIMS m/z 176.10 ([M]⁺).

Example 43: Preparation of4-((Z)-3-(3,4-dichloro-5-vinylphenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N—((R)-1-oxo-1-((2,2,2-trifluoroethyl)amino)propan-2-yl)-2-(trifluoromethyl)benzamide(F186)

Tetrakis(triphenylphosphine)palladium(0) (26.7 mg, 0.023 mmol) was addedto a solution of4-((Z)-3-(3-bromo-4,5-dichlorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N—((R)-1-oxo-1-((2,2,2-trifluoroethyl)amino)propan-2-yl)-2-(trifluoromethyl)benzamide(F185) (0.08 g, 0.12 mmol) in toluene (1.1 mL) at room temperature. Thereaction mixture was degassed by purging with nitrogen (3×10 minutes).Tributyl vinyl stannane (0.11 g, 0.35 mmol) was added to the reactionmixture. The reaction mixture was again degassed by purging withnitrogen (3×10 minutes) and stirred at 110° C. for 12 hours. Thereaction mixture was quenched with water and then extracted with ethylacetate. The organic layer was dried over sodium sulfate, filtered, andconcentrated. Purification by flash column chromatography using 30%ethyl acetate in hexanes provided the title compound as a pale yellowgum (0.0231 g, 30%).

The following compounds were prepared in like manner to the procedureoutlined in Example 43:

4-((Z)-3-(4-Allyl-3,5-dichlorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N—((R)-1-oxo-1-((2,2,2-trifluoroethyl)amino)propan-2-yl)-2-(trifluoromethyl)benzamide(F146)

Isolated as a pale yellow gum (0.115 g, 35%).

4-((Z)-3-(3,5-Dichloro-4-((E)-prop-1-en-1-yl)phenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N—((R)-1-oxo-1-((2,2,2-trifluoroethyl)amino)propan-2-yl)-2-(trifluoromethyl)benzamide(F147)

Isolated as a pale yellow solid (0.135 g, 42%).

4-((Z)-3-(3,5-Dichloro-4-(prop-1-en-2-yl)phenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N—((R)-1-oxo-1-((2,2,2-trifluoroethyl)amino)propan-2-yl)-2-(trifluoromethyl)benzamide(F148)

Isolated as a pale yellow gum (0.181 g, 57%).

4-((Z)-3-(4-Chloro-3,5-divinylphenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N—((R)-1-oxo-1-((2,2,2-trifluoroethyl)amino)propan-2-yl)-2-(trifluoromethyl)benzamide(F184)

Isolated as a yellow oil 0.0444 g, 90%).

4-((Z)-3-(3,4-Dichloro-5-(prop-1-en-2-yl)phenyl)-1,4,4,4-tetrafluoro-but-1-en-1-yl)-N—((R)-1-oxo-1-((2,2,2-trifluoroethyl)amino)propan-2-yl)-2-(trifluoromethyl)benzamide(F187)

Isolated as a yellow oil (0.052 g, 51%).

4-((Z)-3-(3,4-Dichloro-5-((E)-prop-1-en-1-yl)phenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N—((R)-1-oxo-1-((2,2,2-trifluoroethyl)amino)propan-2-yl)-2-(trifluoromethyl)benzamide(F188)

Isolated as a yellow gum (0.092 g, 65%).

4-((Z)-3-(3,4-Dichloro-5-ethynylphenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N—((R)-1-oxo-1-((2,2,2-trifluoroethyl)amino)propan-2-yl)-2-(trifluoromethyl)benzamide(F189)

Isolated as a white gum (0.016 g, 28%).

4-((Z)-3-(3,4-Dichloro-5-(prop-1-yn-1-yl)phenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N—((R)-1-oxo-1-((2,2,2-trifluoroethyl)amino)propan-2-yl)-2-(trifluoromethyl)benzamide(F190)

Isolated as a yellow gum (0.017 g, 29%).

4-((Z)-3-(3,4-Dichloro-5-(3,3-dimethylbut-1-yn-1-yl)phenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N—((R)-1-oxo-1-((2,2,2-trifluoroethyl)amino)propan-2-yl)-2-(trifluoromethyl)benzamide(F191)

Isolated as a yellow gum (0.010 g, 19%).

4-((Z)-3-(3,4-Dichloro-5-cyanophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N—((R)-1-oxo-1-((2,2,2-trifluoroethyl)amino)propan-2-yl)-2-(trifluoromethyl)benzamide(F192)

Isolated as a colorless oil (0.035 g, 52%).

4-((Z)-3-(3-Chloro-5-(3,3-dimethylbut-1-yn-1-yl)phenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N—((R)-1-oxo-1-((2,2,2-trifluoroethyl)amino)propan-2-yl)-2-(trifluoromethyl)benzamide(F212)

Isolated as a yellow gum (0.083 g, 87%).

4-((Z)-3-(3-(3,3-Dimethylbut-1-yn-1-yl)-4,5-difluorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N—((R)-1-oxo-1-((2,2,2-trifluoroethyl)amino)propan-2-yl)-2-(trifluoromethyl)benzamide(F216)

Isolated as an orange oil (0.038 g, 59%).

Example 44: Preparation of(Z)-4-(3-(3,4-difluorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)-2-(trifluoromethyl)benzamide(F215)

Dichlorobis(triphenylphosphine)palladium(II) (18.93 mg, 0.027 mmol) wasadded to a solution of4-((Z)-3-(3-bromo-4,5-dicflurorphenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N—((R)-1-oxo-1-((2,2,2-trifluoroethyl)amino)propan-2-yl)-2-(trifluoromethyl)benzamide(F185) (0.087 g, 0.135 mmol) in toluene (0.674 mL) at room temperature.The reaction mixture was degassed by purging with nitrogen (3×10minutes). 2-(Tributylstannyl)pyridine (99 mg, 0.270 mmol) was added intothe reaction mixture. The reaction mixture was again degassed by purgingwith nitrogen (3×10 minutes) and stirred at 110° C. for 4 hours. Thereaction mixture was loaded directly onto a column with dichloromethaneand methanol. Purification by flash column chromatography provided thetitle compound as an orange oil (0.011 g, 15%).

Example 45 Preparation of4-((Z)-3-(3,4-dichloro-5-formylphenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N—((R)-1-oxo-1-((2,2,2-trifluoroethyl)amino)propan-2-yl)-2-(trifluoromethyl)benzamide(C185)

Osmium tetraoxide (2.5% in tert-butanol; 48 mg, 0.005 mmol) was added toa solution of4-((Z)-3-(3,4-dichloro-5-vinylphenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N—((R)-1-oxo-1-((2,2,2-trifluoroethyl)amino)propan-2-yl)-2-(trifluoromethyl)benzamide(F186) (0.06 g, 0.094 mmol) in tetrahydrofuran-water (2:1, 1.1 mL) atroom temperature. The reaction mixture was stirred for 5 minutes. Sodiumperiodate (0.061 g, 0.282 mmol) was added to the reaction mixture. Thereaction mixture was stirred at 20° C. for 12 hours. The reactionmixture was quenched with sodium bisulfate (100 mg) and then extractedwith ethyl acetate (10 mL). The organic layer was dried over sodiumsulfate, filtered, and concentrated. Purification by flash columnchromatography using 40% ethyl acetate in hexanes provided the titlecompound as a pale yellow gum (0.050 g, 75%): ¹H NMR (400 MHz, CDCl₃) δ10.47 (s, 1H), 7.87 (dd, J=12.8, 1.9 Hz, 2H), 7.81-7.70 (m, 2H),7.60-7.49 (m, 1H), 7.34 (d, J=6.5 Hz, 1H), 6.83 (d, J=7.6 Hz, 1H),5.99-5.79 (m, 1H), 4.92-4.78 (m, 1H), 4.71 (p, J=9.0 Hz, 1H), 3.85(dddd, J=15.2, 12.9, 7.6, 3.5 Hz, 2H), 1.51 (d, J=7.0 Hz, 3H); ¹⁹F NMR(376 MHz, CDCl₃) δ −58.18, −68.49, −72.97, −110.05; ESIMS m/z 639([M−H]⁻).

The following compounds were prepared in like manner to the procedureoutlined in Example 45:

4-((Z)-3-(3,4-Dichloro-5-formylphenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N—((R)-3-oxo-2-(2,2,2-trifluoroethyl)isoxazolidin-4-yl)-2-(trifluoromethyl)benzamide(C186)

Isolated as a white gum (0.074 g, 88%): ¹H NMR (400 MHz, CDCl₃) δ 10.47(s, 1H), 7.88 (dd, J=5.8, 1.9 Hz, 2H), 7.81-7.72 (m, 2H), 7.63 (d, J=8.1Hz, 1H), 6.70-6.57 (m, 1H), 6.01-5.80 (m, 1H), 5.08-4.86 (m, 2H),4.79-4.61 (m, J=9.3 Hz, 1H), 4.30-3.98 (m, 3H); ¹⁹F NMR (376 MHz, CDCl₃)δ −59.08 (d, J=2.0 Hz), −68.49, −70.35 (d, J=3.9 Hz), −112.33; ESIMS m/z655 ([M−H]⁻).

4-((Z)-3-(3-Chloro-5-formylphenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N—((R)-1-oxo-1-((2,2,2-trifluoroethyl)amino)propan-2-yl)-2-(trifluoromethyl)benzamide(C187)

Isolated as an orange solid (0.800 g, 54%): ¹H NMR (400 MHz, CDCl₃) δ10.00 (d, J=0.6 Hz, 1H), 7.91-7.86 (m, 3H), 7.81 (d, J=5.6 Hz, 1H), 7.66(s, 1H), 7.57 (d, J=8.1 Hz, 1H), 7.02 (t, J=6.4 Hz, 1H), 6.59 (d, J=7.6Hz, 1H), 5.92 (dd, J=32.6, 9.6 Hz, 1H), 4.89-4.66 (m, 2H), 3.88 (ddd,J=19.5, 9.2, 6.5 Hz, 2H), 1.51 (d, J=7.0 Hz, 3H); ¹⁹F NMR (376 MHz,CDCl₃) δ −59.28, −68.39, −70.36, −110.05; ESIMS m/z 606 ([M−H]⁻).

Example 46: Preparation of4-((Z)-3-(3,4-dichloro-5-(hydroxymethyl)phenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N—((R)-1-oxo-1-((2,2,2-trifluoroethyl)amino)propan-2-yl)-2-(trifluoromethyl)benzamide(C188)

Sodium borohydride (18 mg, 0.468 mmol) was added to a solution of4-((Z)-3-(3,4-dichloro-5-formylphenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N—((R)-1-oxo-1-((2,2,2-trifluoroethyl)amino)propan-2-yl)-2-(trifluoromethyl)benzamide(C185) (0.2 g, 0.312 mmol) in tetrahydrofuran (1.5 mL) at roomtemperature. The reaction mixture was stirred at 20° C. for 12 hours.The reaction mixture was quenched with water (5 mL) and then extractedwith ethyl acetate (50 mL). The organic layer was dried over sodiumsulfate, filtered, and concentrated. Purification by flash columnchromatography using 35% ethyl acetate in hexanes provided the titlecompound as a pale yellow gum (0.110 g, 52%): ¹H NMR (400 MHz, CDCl₃) δ7.80 (t, J=2.0 Hz, 1H), 7.72 (d, J=6.7 Hz, 1H), 7.67 (dt, J=8.1, 1.7 Hz,1H), 7.52 (d, J=2.0 Hz, 1H), 7.47-7.41 (m, 2H), 7.31 (d, J=7.2 Hz, 1H),6.03-5.70 (m, 1H), 4.87 (p, J=7.1 Hz, 1H), 4.74 (s, 2H), 4.64 (p, J=9.0Hz, 1H), 3.90-3.66 (m, 2H), 3.38 (s, 1H), 1.48 (dd, J=7.0, 2.6 Hz, 3H);¹⁹F NMR (376 MHz, CDCl₃) δ −58.48, −67.37, −72.66, −110.57; ESIMS m/z641 ([M−H]⁻).

Example 47: Preparation of4-((Z)-3-(3,4-dichloro-5-(difluoromethyl)phenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N—((R)-1-oxo-1-((2,2,2-trifluoroethyl)amino)propan-2-yl)-2-(trifluoromethyl)benzamide(F195)

Bis(2-methoxyethyl)aminosulfur trifluoride (35 mg, 0.16 mmol) was addedto a solution of4-((Z)-3-(3,4-dichloro-5-formylphenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N—((R)-1-oxo-1-((2,2,2-trifluoroethyl)amino)propan-2-yl)-2-(trifluoromethyl)benzamide(C185) (0.05 g, 0.078 mmol) in dichloromethane (0.5 mL) at roomtemperature. One drop of methanol was added and the reaction mixture wasstirred at 20° C. for 12 hours. The reaction mixture was quenched withwater (5 mL) and then extracted with ethyl acetate (15 mL). The organiclayer was dried over sodium sulfate, filtered, and concentrated.Purification by flash column chromatography using 35% ethyl acetate inhexanes provided the title compound as a white wax (0.028 g, 51%).

The following compounds were prepared in like manner to the procedureoutlined in Example 47:

4-((Z)-3-(3,4-Dichloro-5-(fluoromethyl)phenyl)-1,4,4,4-tetrafluoro-but-1-en-1-yl]-N—((R)-1-oxo-1-(2,2,2-trifluoroethyl)amino)propan-2-yl]-2-(trifluoromethyl)benzamide(F194)

Isolated as a colorless gum (0.0931 g, 67%).

4-((Z)-3-(3,4-Dichloro-5-(difluoromethyl)phenyl)-1,4,4,4-tetrafluoro-but-1-enyl)-N—((R)-3-oxo-2-(2,2,2-trifluoroethyl)isoxazolidin-4-yl)-2-(trifluoromethyl)benzamide(F199)

Isolated as a yellow gum (0.040 g, 53%).

4-((Z)-3-(3-Chloro-5-(difluoromethyl)phenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N—((R)-1-oxo-1-((2,2,2-trifluoroethyl)amino)propan-2-yl)-2-(trifluoromethyl)benzamide(F213)

Isolated as an orange solid (0.062 g, 76%).

Methyl 3,5-dichloro-4-(difluoromethyl)benzoate (C189)

Isolated as a pale yellow solid (0.70 g, 63%): ¹H NMR (300 MHz, DMSO-d₆)δ 8.02 (s, 2H), 7.50 (t, J=52.2 Hz, 1H), 3.99 (s, 3H); ESIMS m/z 254.2([M]⁺).

Example 48: Preparation of4-((Z)-3-(3-chloro-5-(2,2,2-trifluoroethoxy)phenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N—((R)-1-oxo-1-((2,2,2-trifluoroethyl)amino)propan-2-yl)-2-(trifluoromethyl)benzamide(F207)

4-((Z)-3-(3-Chloro-5-hydroxyphenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N—((R)-1-oxo-1-((2,2,2-trifluoroethyl)amino)propan-2-yl)-2-(trifluoromethyl)benzamide(C163) (0.070 g, 0.118 mmol) was dissolved in acetone (1.177 mL) andpotassium carbonate (0.049 g, 0.353 mmol) and 2,2,2-trifluoroethyltrifluoromethanesulfonate (0.025 mL, 0.177 mmol) were addedsequentially. The reaction mixture was stirred overnight. The solventwas removed. Purification of the residue on silica gel eluting with0-30% acetone in hexanes provided the title compound as a clearcolorless oil (0.016 g, 20.1%).

The following compounds were prepared in like manner to the procedureoutlined in Example 48:

4-((Z)-3-(3-Bromo-4-(trifluoromethyl)phenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N—((R)-1-oxo-1-((2,2,2-trifluoroethyl)amino)propan-2-yl)-2-(trifluoromethyl)benzamide(F208)

Isolated as an orange oil (0.107 g, 55.6%).

(Z)-4-(3-(3-Bromo-4-(trifluoromethyl)phenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)-2-(trifluoromethyl)benzamide(F209)

Isolated as an off-white foam (0.116 g, 55.4%).

Example 49: Preparation of(Z)—N-(2-(ethyl(2,2,2-trifluoroethyl)amino)-2-oxoethyl)-4-(1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide(F167)

To a stirred solution of(Z)-4-(1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzoicacid (C2) (0.167 g, 0.34 mmol) in N,N-dimethylformamide (4 mL) wereadded(1-cyano-2-ethoxy-2-oxoethylidenaminooxy)dimethylamino-morpholino-carbeniumhexafluorophosphate (0.170 g, 0.40 mmol) and N-methyl morpholine (0.10mL, 0.92 mmol). After 15 minutes the reaction mixture was treated with2-amino-N-ethyl-N-(2,2,2-trifluoroethyl)acetamide hydrochloride (C171)(0.104 g, 0.47 mmol) and was stirred for 20 hours at room temperature.The mixture was partitioned between diethyl ether and 5% aqueous sodiumbisulfate. The organic layer was washed with 5% aqueous sodium bisulfate(2×), saturated aqueous sodium carbonate and brine, then dried overmagnesium sulfate and concentrated under reduced pressure to affordcrude compound. The crude compound was purified by column chromatography(SiO₂) to afford the title compound as a yellow/orange gum (0.127 g,56%).

The following compound was prepared in like manner to the procedureoutlined in Example 49:

tert-Butyl(Z)-(4-(1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzoyl)glycinate(C190)

Isolated as a brown foam (0.300 g, 42%): ¹H NMR (400 MHz, CDCl₃) δ 7.85(s, 1H), 7.80-7.73 (m, 1H), 7.64 (d, J=4.3 Hz, 1H), 7.44 (s, 2H), 6.37(t, J=5.0 Hz, 1H), 5.83 (dd, J=32.5, 9.5 Hz, 1H), 4.68-4.54 (m, 1H),4.11 (d, J=4.9 Hz, 2H), 1.50 (s, 9H); ESIMS m/z 610 ([M+H]⁺).

Example 50: Preparation ofN—((R)-1-((3,3-difluorocyclobutyl)amino)-1-oxopropan-2-yl)-4-((Z)-1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide(F168)

To a stirred solution of(Z)-4-(1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzoicacid (C2) (0.250 g, 0.50 mmol) and(R)-2-amino-N-(3,3-difluorocyclobutyl)propanamide hydrochloride (C172)(0.162 g, 0.75 mmol) in methylene chloride (5 mL) were added1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.114 g,0.59 mmol), 4-dimethylaminopyridine (0.75 g, 0.67 mmol) andtriethylamine (0.20 mL, 1.43 mmol). After 20 hours the reaction mixturewas diluted with methylene chloride (20 mL) and washed with 5% aqueoussodium bisulfate (3×), saturated aqueous sodium carbonate (2×) andbrine. The combined organic extracts were dried over magnesium sulfateand concentrated under reduced pressure to afford crude compound. Thecrude compound was purified by column chromatography (SiO₂, eluting with0-45% ethyl acetate gradient in hexanes) to afford the title compound asa yellow oil (0.045 g, 14%).

Example 51: Preparation of(Z)-2-(4-(1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)phenylthioamido)-N-(2,2,2-trifluoroethyl)acetamide(PF82)

To(Z)-(4-(1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)phenylcarbonothioyl)glycine(C177) (0.044 g, 0.077 mmol) and2-(1H-benzo[d][1,2,3]triazol-1-yl)-1,1,3,3-tetramethylisouroniumhexafluorophosphate(V) (0.041 g, 0.108 mmol) in N,N-dimethylformamide(0.3 mL) was added 2,2,2-trifluoroethanamine (0.015 mL, 0.186 mmol). Themixture was stirred for 2 hours at room temperature and then partitionedbetween ethyl acetate and water. The organic layer was washed withwater, 0.1 N aqueous hydrochloric acid solution, and brine, andconcentrated under reduced pressure to afford crude compound. The crudecompound was purified by column chromatography (SiO₂, eluting with0-100% ethyl acetate gradient in hexanes) to afford the title compoundas a yellow foam (0.025 g, 45%).

Example 52: Preparation of(Z)-4-(1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-N-(2-thioxo-2-((2,2,2-trifluoroethyl)amino)ethyl)-2-(trifluoromethyl)benzothioamide(PF88) and(Z)-4-(1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-N-(2-thioxo-2-((2,2,2-trifluoroethyl)amino)ethyl)-2-(trifluoromethyl)benzamide(PF94)

A 5 mL microwave reactor vial was charged with(Z)—N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)-4-(1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide(F1) (0.11 g, 0.174 mmol) and2,4-bis(4-methoxyphenyl)-1,3,2,4-dithiadiphosphetane 2,4-disulfide(0.070 g, 0.174 mmol) in dichloroethane (3 mL). The mixture was placedin a microwave reactor and heated to 130° C. for 30 min. After coolingto room temperature, the reaction mixture was diluted withdichloromethane and washed with aqueous saturated sodium bicarbonatesolution (2×). The organic phase was dried with sodium sulfate,filtered, and concentrated. Purification by column chromatography (SiO₂,eluting with 0-100% ethyl acetate gradient in hexanes) afforded thetitle compounds, (PF88) as a pale yellow glass (0.045 g, 31%) and (PF94)as a yellow glass (0.025 g, 20%).

Example 53: Preparation of tert-butyl(2-((2-hydroxy-2-methylpropyl)amino)-2-oxoethyl)carbamate (C191)

To a stirred solution of (tert-butoxycarbonyl)glycine (0.500 g, 2.85mmol) in tetrahydrofuran (30 mL) cooled in a −78° C. bath was addedN-methyl morpholine (0.433 g, 4.28 mmol). After 15 minutes isobutylchloroformate (0.585 g, 4.28 mmol) was added. After an additional 15minutes of stirring in a −78° C. bath the reaction mixture was treatedwith 1-amino-2-methyl-propan-2-ol (0.279 g, 3.14 mmol). The mixture wasstirred an additional 1 hour at which time the reaction mixture wasdiluted with water. The mixture was extracted with ethyl acetate. Theorganic layer was washed with brine, dried over sodium sulfate andconcentrated under reduced pressure to afford crude compound.Purification by column chromatography (SiO₂, eluting with 40% ethylacetate in petroleum ether) afforded the title compound as a colorlessliquid (0.7 g, 70%): ¹H NMR (400 MHz, CDCl₃) δ 6.55 (br s, 1H), 5.18 (brs, 1H), 3.86-3.80 (m, 2H), 3.29-3.28 (m, 2H), 1.45 (s, 6H), 1.22 (s,9H); IR (thin film) 3335, 1698, 1275 cm⁻¹; ESIMS m/z 247.30 ([M+H]⁺).

The following compound was prepared in like manner to the procedureoutlined in Example 53:

tert-Butyl (2-oxo-2-((2-oxopropyl)amino)ethyl)carbamate (C192)

Isolated as a colorless oil (0.60 g, 78%): ¹H NMR (300 MHz, CDCl₃) δ6.75 (br s, 1H), 5.13 (br s, 1H), 4.18-4.16 (m, 2H), 3.85-3.83 (m, 2H),2.21 (s, 3H), 1.46 (s, 9H); IR (thin film) 3345, 1704, 1169 cm⁻¹; ESIMSm/z 131.20 ([M−CO₂C₄H]⁻).

Example 54: Preparation of tert-butyl1-methyl-2-(2,2,2-trifluoroethyl)hydrazine-1-carboxylate (C193)

To a stirred solution of tert-butyl2-(2,2,2-trifluoroethyl)hydrazine-1-carboxylate (2.00 g, 9.34 mmol) inN,N-dimethylformamide (20 mL) cooled in an ice bath was added sodiumhydride (0.450 g, 18.7 mmol). After 20 minutes the mixture was treatedwith methyl iodide (1.99 g, 14.0 mmol) and stirred for an additional 2hours with cooling. The reaction mixture was then poured into ice waterand extracted with ethyl acetate. The organic layer was washed withbrine, dried over sodium sulfate and concentrated under reduced pressureto afford crude compound. Purification by column chromatography (SiO₂)afforded the title compound as a yellow oil (1.8 g, 85%): ¹H NMR (400MHz, CDCl₃) δ 4.29 (br s, 1H), 3.49-3.46 (m, 2H), 3.03 (s, 3H), 1.47 (s,9H).

Example 55: Preparation of tert-butyl1,2-dimethyl-2-(2,2,2-trifluoroethyl)hydrazine-1-carboxylate (C194)

To a stirred solution of tert-butyl2-(2,2,2-trifluoroethyl)hydrazine-1-carboxylate (1.00 g, 4.67 mmol) inN,N-dimethylformamide (10 mL) cooled in an ice bath were addedsequentially sodium hydride (0.34 g, 14 mmol) and methyl iodide (1.99 g,14 mmol). The mixture was allowed to warm to room temperature and stirfor 12 hours. The reaction mixture was poured into ice water andextracted with ethyl acetate. The organic layer was washed with brine,dried over sodium sulfate and concentrated under reduced pressure toafford crude compound. Purification by column chromatography (SiO₂)afforded the title compound as a yellow oil (1.0 g, 88%): ¹H NMR (300MHz, DMSO-d₆) δ 3.63-3.45 (m, 2H), 2.88 (s, 3H), 2.67 (m, 3H), 1.35 (s,9H); IR (thin film) 3422, 1694, 769 cm⁻¹.

Example 56: PreparationN-(2-(ethyl(2,2,2-trifluoroethyl)amino)-2-oxoethyl)-3,3-dimethylbutanamide(C195)

To a stirred solution of (tert-butoxycarbonyl)glycine (0.528 g, 3.01mmol) in N,N-dimethylformamide (5 mL) cooled in an ice bath was added(1-cyano-2-ethoxy-2-oxoethylidenaminooxy)dimethylamino-morpholino-carbeniumhexafluorophosphate (1.88 g, 4.39 mmol) and diisopropylethylamine (0.60mL, 3.45 mmol). After 15 minutes the reaction mixture was treated withN-ethyl-2,2,2-trifluoroethanamine hydrochloride (0.510 g, 3.11 mmol) anddiisopropylethylamine (0.60 mL, 3.11 mmol) in N,N-dimethylformamide (2mL). The mixture was allowed to warm to room temperature and was stirredfor 20 hours. The mixture was partitioned between diethyl ether and 5%aqueous sodium bisulfate. The organic layer was washed with 5% aqueoussodium bisulfate (2×), saturated aqueous sodium carbonate and brine,dried over magnesium sulfate, and concentrated under reduced pressure toafford the title compound as a red solid (0.710 g, 83%): mp 70-72° C.;¹H NMR (400 MHz, CDCl₃) δ 5.44 (s, 1H), 4.20-3.91 (m, 4H), minor rotamer3.83 (q, J=8.4 Hz, 2H), minor rotamer 3.53 (q, J=7.1 Hz, 2H), majorrotamer 3.44 (q, J=7.2 Hz, 2H), 1.45 (s, 9H), major rotamer 1.24 (t,J=7.2 Hz, 3H), minor rotamer 1.16 (t, J=7.1 Hz, 3H); ¹⁹F NMR (376 MHz,CDCl₃) δ major rotamer −69.57, minor rotamer −70.06; ESIMS m/z 228([M-C₄H₉]⁺).

Example 57: Preparation of tert-butyl(R)-(1-oxo-1-(2-(2,2,2-trifluoroethyl)hydrazinyl)propan-2-yl)carbamate(C196)

Diisopropylethylamine (2.26 mL, 13.2 mmol),2-chloro-1,3-dimethylimidazolidinium hexafluorophosphate (1.47 g, 5.29mmol), and 1-hydroxy-7-azabenzotriazole (0.72 g, 5.29 mmol) were addedto a solution of (tert-butoxycarbonyl)-D-alanine (1.00 g, 5.29 mmol) and2-(2,2,2-trifluoroethyl)hydrazine hydrochloride (0.80 g, 0.5.29 mmol) inN,N-dimethylformamide (10 mL) at room temperature. The mixture wasstirred for 12 hours then was diluted with dichloromethane. The organiclayer was washed sequentially with a 2 N hydrochloric acid solution, 2 Naqueous sodium bicarbonate, water, and then brine. The organic layer wasthen dried over sodium sulfate, filtered, and concentrated. Purificationby column chromatography (SiO₂) provided the title compound as a whitesolid (0.60 g, 37%): ¹H NMR (300 MHz, DMSO-d₆) δ 9.45 (s, 1H), 6.82 (d,J=7.2 Hz, 1H), 5.57 (d, J=4.50 Hz, 1H), 3.92-3.85 (m, 1H), 3.42-3.31 (m,2H), 1.36 (s, 9H), 1.14 (d, J=6.9 Hz, 3H); IR (thin film) 3342, 1683cm⁻¹; ESIMS m/z 284.40 ([M−H]⁻).

The following compounds were prepared in like manner to the procedureoutlined in Example 57:

tert-Butyl(R)-(1-(1-methyl-2-(2,2,2-trifluoroethyl)hydrazinyl)-1-oxopropan-2-yl)carbamate (C197)

Isolated as a yellow gum (0.90 g, 47%): ¹H NMR (300 MHz, DMSO-d₆) δ 6.56(d, J=8.1 Hz, 1H), 5.74 (br s, 1H), 4.83-4.78 (m, 1H), 3.65-3.58 (m,2H), 2.96 (s, 3H), 1.35 (s, 9H), 1.13 (d, J=7.2 Hz, 3H); IR (thin film)3419, 1698, 1167 cm⁻¹; ESIMS m/z 300.30 ([M−H]⁻).

tert-Butyl(R)-(1-(1,2-dimethyl-2-(2,2,2-trifluoroethyl)hydrazinyl)-1-oxopropan-2-yl)carbamate(C198)

Isolated as a yellow oil (0.50 g, 50%): ¹H NMR (300 MHz, DMSO-d₆) δ 6.95(br s, 1H), 4.95-4.78 (m, 1H), 3.77-3.31 (m, 2H), 2.84 (s, 3H), 2.64 (m,3H), 1.35 (s, 9H), 1.13 (d, J=6.9 Hz, 3H); IR (thin film) 2979, 1709,1168 cm⁻¹; ESIMS m/z 213.96 ([M−CO₂C₄H₉]⁻).

Example 58: Preparation of1-(3,4-dichloro-5-methylphenyl)-2,2,2-trifluoroethan-1-one (C201)

To 5-bromo-1,2-dichloro-3-methylbenzene (6.9 g, 29 mmol) intetrahydrofuran (65 mL) cooled in an ice bath under nitrogen was addedisopropylmagnesium chloride lithium chloride complex in tetrahydrofuran(26.8 mL, 34.8 mmol). After 1 hour methyl 2,2,2-trifluoroacetate (3.79mL, 37.7 mmol) was added. After 30 minutes, the ice bath was removed,and the solution was stirred for 1 hour. The reaction mixture wasquenched with aqueous hydrochloric acid (2 N). The mixture wasconcentrated and extracted with dichloromethane. The organic layer waswashed with brine, dried over sodium sulfate, filtered, andconcentrated. Purification by column chromatography (SiO₂, petroleumether) provided the title compound as a white solid (5.9 g, 80%): ¹H NMR(400 MHz, CDCl₃) δ 8.00 (s, 1H), δ 7.83 (s, 1H), 2.51 (s, 3H); EIMS m/z256 ([M]⁺).

Biological Assays

The following bioassays against Beet Armyworm (Spodoptera exigua),Cabbage Looper (Trichoplusia ni), Corn Earworm (Helicoverpa zea), GreenPeach Aphid (Myzus persicae), and Yellow Fever Mosquito (Aedes aegypti),are included herein due to the damage they inflict. Furthermore, theBeet Armyworm, Corn Earworm, and Cabbage Looper are three good indicatorspecies for a broad range of chewing pests. Additionally, the GreenPeach Aphid is a good indicator species for a broad range of sap-feedingpests. The results with these four indicator species along with theYellow Fever Mosquito show the broad usefulness of the molecules ofFormula One in controlling pests in Phyla Arthropoda, Mollusca, andNematoda (For further information see Methods for the Design andOptimization of New Active Ingredients, Modern Methods in CropProtection Research, Edited by Jeschke, P., Kramer, W., Schirmer, U.,and Matthias W., p. 1-20, 2012).

Example A: Bioassays on Beet Armyworm (Spodoptera exigua, LAPHEG)(“BAW”), Corn Earworm (Helicoverpa zea, HELIZE) (“CEW”), and CabbageLooper (Trichoplusia ni, TRIPNI) (“CL”)

Beet armyworm is a serious pest of economic concern for alfalfa,asparagus, beets, citrus, corn, cotton, onions, peas, peppers, potatoes,soybeans, sugar beets, sunflowers, tobacco, tomatoes, among other crops.It is native to Southeast Asia but is now found in Africa, Australia,Japan, North America, and Southern Europe. The larvae may feed in largeswarms causing devastating crop losses. It is known to be resistant toseveral pesticides.

Cabbage looper is a serious pest found throughout the world. It attacksalfalfa, beans, beets, broccoli, Brussel sprouts, cabbage, cantaloupe,cauliflower, celery, collards, cotton, cucumbers, eggplant, kale,lettuce, melons, mustard, parsley, peas, peppers, potatoes, soybeans,spinach, squash, tomatoes, turnips, and watermelons, among other crops.This species is very destructive to plants due to its voraciousappetite. The larvae consume three times their weight in food daily. Thefeeding sites are marked by large accumulations of sticky, wet, fecalmaterial. It is known to be resistant to several pesticides.

Corn earworm is considered by some to be the most costly crop pest inNorth America. It often attacks valuable crops, and the harvestedportion of the crop. This pest damages alfalfa, artichoke, asparagus,cabbage, cantaloupe, collard, corn, cotton, cowpea, cucumber, eggplant,lettuce, lima bean, melon, okra, pea, pepper, potato, pumpkin, snapbean, soybean, spinach, squash, sugarcane, sweet potato, tomato, andwatermelon, among other crops. Furthermore, this pest is also known tobe resistant to certain insecticides.

Consequently, because of the above factors control of these pests isimportant. Furthermore, molecules that control these pests (BAW, CEW,and CL), which are known as chewing pests, are useful in controllingother pests that chew on plants.

Certain molecules disclosed in this document were tested against BAW,CEW, and CL using procedures described in the following examples. In thereporting of the results, the “BAW, CEW, & CL Rating Table” was used(See Table Section).

Bioassays on BAW

Bioassays on BAW were conducted using a 128-well diet tray assay. One tofive second instar BAW larvae were placed in each well (3 mL) of thediet tray that had been previously filled with 1 mL of artificial dietto which 50 μg/cm² of the test molecule (dissolved in 50 μL of 90:10acetone-water mixture) had been applied (to each of eight wells) andthen allowed to dry. Trays were covered with a clear self-adhesive coverand held at 25° C., 14:10 light-dark for five to seven days. Percentmortality was recorded for the larvae in each well; activity in theeight wells was then averaged. The results are indicated in the tableentitled “Table ABC: Biological Results” (See Table Section).

Bioassays on CL

Bioassays on CL were conducted using a 128-well diet tray assay. One tofive second instar CL larvae were placed in each well (3 mL) of the diettray that had been previously filled with 1 mL of artificial diet towhich 50 μg/cm² of the test molecule (dissolved in 50 μL of 90:10acetone-water mixture) had been applied (to each of eight wells) andthen allowed to dry. Trays were covered with a clear self-adhesive coverand held at 25° C., 14:10 light-dark for five to seven days. Percentmortality was recorded for the larvae in each well; activity in theeight wells was then averaged. The results are indicated in the tableentitled “Table ABC: Biological Results” (See Table Section).

Example B: Bioassays on Green Peach Aphid (Myzus persicae, MYZUPE)(“GPA”)

GPA is the most significant aphid pest of peach trees, causing decreasedgrowth, shriveling of the leaves, and the death of various tissues. Itis also hazardous because it acts as a vector for the transport of plantviruses, such as potato virus Y and potato leafroll virus to members ofthe nightshade/potato family Solanaceae, and various mosaic viruses tomany other food crops. GPA attacks such plants as broccoli, burdock,cabbage, carrot, cauliflower, daikon, eggplant, green beans, lettuce,macadamia, papaya, peppers, sweet potatoes, tomatoes, watercress, andzucchini, among other crops. GPA also attacks many ornamental crops suchas carnation, chrysanthemum, flowering white cabbage, poinsettia, androses. GPA has developed resistance to many pesticides. Consequently,because of the above factors control of this pest is important.Furthermore, molecules that control this pest (GPA), which is known as asap-feeding pest, are useful in controlling other pests that feed on thesap from plants.

Certain molecules disclosed in this document were tested against GPAusing procedures described in the following example. In the reporting ofthe results, the “GPA & YFM Rating Table” was used (See Table Section).

Cabbage seedlings grown in 3-inch pots, with 2-3 small (3-5 cm) trueleaves, were used as test substrate. The seedlings were infested with20-50 GPA (wingless adult and nymph stages) one day prior to chemicalapplication. Four pots with individual seedlings were used for eachtreatment. Test molecules (2 mg) were dissolved in 2 mL ofacetone/methanol (1:1) solvent, forming stock solutions of 1000 ppm testmolecule. The stock solutions were diluted 5× with 0.025% Tween 20 inwater to obtain the solution at 200 ppm test molecule. A hand-heldaspirator-type sprayer was used for spraying a solution to both sides ofcabbage leaves until runoff. Reference plants (solvent check) weresprayed with the diluent only containing 20% by volume ofacetone/methanol (1:1) solvent. Treated plants were held in a holdingroom for three days at approximately 25° C. and ambient relativehumidity (RH) prior to grading. Evaluation was conducted by counting thenumber of live aphids per plant under a microscope. Percent Control wasmeasured by using Abbott's correction formula (W. S. Abbott, “A Methodof Computing the Effectiveness of an Insecticide” J. Econ. Entomol. 18(1925), pp. 265-267) as follows.

Corrected % Control=100*(X−Y)/X

-   -   where    -   X=No. of live aphids on solvent check plants and    -   Y=No. of live aphids on treated plants

The results are indicated in the table entitled “Table ABC: BiologicalResults” (See Table Section).

Example C: Bioassays on Yellow Fever Mosquito (Aedes aegypti, AEDSAE)(“YFM”)

YFM prefers to feed on humans during the daytime and is most frequentlyfound in or near human habitations. YFM is a vector for transmittingseveral diseases. It is a mosquito that can spread the dengue fever andyellow fever viruses. Yellow fever is the second most dangerousmosquito-borne disease after malaria. Yellow fever is an acute viralhemorrhagic disease and up to 50% of severely affected persons withouttreatment will die from yellow fever. There are an estimated 200,000cases of yellow fever, causing 30,000 deaths, worldwide each year.Dengue fever is a nasty, viral disease; it is sometimes called“breakbone fever” or “break-heart fever” because of the intense pain itcan produce. Dengue fever kills about 20,000 people annually.Consequently, because of the above factors control of this pest isimportant. Furthermore, molecules that control this pest (YFM), which isknown as a sucking pest, are useful in controlling other pests thatcause human and animal suffering.

Certain molecules disclosed in this document were tested against YFMusing procedures described in the following paragraph. In the reportingof the results, the “GPA & YFM Rating Table” was used (See TableSection).

Master plates containing 400 μg of a molecule dissolved in 100 μL ofdimethyl sulfoxide (DMSO) (equivalent to a 4000 ppm solution) are used.A master plate of assembled molecules contains 15 μL per well. To thisplate, 135 μL of a 90:10 water:acetone mixture is added to each well. Arobot (Biomek® NXP Laboratory Automation Workstation) is programmed todispense 15 μL aspirations from the master plate into an empty 96-wellshallow plate (“daughter” plate). There are 6 reps (“daughter” plates)created per master. The created daughter plates are then immediatelyinfested with YFM larvae.

The day before plates are to be treated, mosquito eggs are placed inMillipore water containing liver powder to begin hatching (4 g. into 400mL). After the daughter plates are created using the robot, they areinfested with 220 μL of the liver powder/larval mosquito mixture (about1 day-old larvae). After plates are infested with mosquito larvae, anon-evaporative lid is used to cover the plate to reduce drying. Platesare held at room temperature for 3 days prior to grading. After 3 days,each well is observed and scored based on mortality. The results areindicated in the table entitled “Table ABC: Biological Results” (SeeTable Section).

Agriculturally Acceptable Acid Addition Salts, Salt Derivatives,Solvates, Ester Derivatives, Polymorphs, Isotopes, and Radionuclides

Molecules of Formula One may be formulated into agriculturallyacceptable acid addition salts. By way of a non-limiting example, anamine function can form salts with hydrochloric, hydrobromic, sulfuric,phosphoric, acetic, benzoic, citric, malonic, salicylic, malic, fumaric,oxalic, succinic, tartaric, lactic, gluconic, ascorbic, maleic,aspartic, benzenesulfonic, methanesulfonic, ethanesulfonic,hydroxyl-methanesulfonic, and hydroxyethanesulfonic acids. Additionally,by way of a non-limiting example, an acid function can form saltsincluding those derived from alkali or alkaline earth metals and thosederived from ammonia and amines. Examples of preferred cations includesodium, potassium, and magnesium.

Molecules of Formula One may be formulated into salt derivatives. By wayof a non-limiting example, a salt derivative may be prepared bycontacting a free base with a sufficient amount of the desired acid toproduce a salt. A free base may be regenerated by treating the salt witha suitable dilute aqueous base solution such as dilute aqueous sodiumhydroxide, potassium carbonate, ammonia, and sodium bicarbonate. As anexample, in many cases, a pesticide, such as 2,4-D, is made morewater-soluble by converting it to its dimethylamine salt.

Molecules of Formula One may be formulated into stable complexes with asolvent, such that the complex remains intact after the non-complexedsolvent is removed. These complexes are often referred to as “solvates.”However, it is particularly desirable to form stable hydrates with wateras the solvent.

Molecules of Formula One may be made into ester derivatives. These esterderivatives can then be applied in the same manner as the moleculesdisclosed in this document is applied.

Molecules of Formula One may be made as various crystal polymorphs.Polymorphism is important in the development of agrochemicals sincedifferent crystal polymorphs or structures of the same molecule can havevastly different physical properties and biological performances.

Molecules of Formula One may be made with different isotopes. Ofparticular importance are molecules having ²H (also known as deuterium)or ³H (also known as tritium) in place of 1H. Molecules of Formula Onemay be made with different radionuclides. Of particular importance aremolecules having ¹⁴C. Molecules of Formula One having deuterium,tritium, or ¹⁴C may be used in biological studies allowing tracing inchemical and physiological processes and half-life studies, as well as,MoA studies.

Stereoisomers

Molecules of Formula One may exist as one or more stereoisomers. Thus,certain molecules may be produced as racemic mixtures. It will beappreciated by those skilled in the art that one stereoisomer may bemore active than the other stereoisomers. Individual stereoisomers maybe obtained by known selective synthetic procedures, by conventionalsynthetic procedures using resolved starting materials, or byconventional resolution procedures. Certain molecules disclosed in thisdocument can exist as two or more isomers. The various isomers includegeometric isomers, diastereomers, and enantiomers. Thus, the moleculesdisclosed in this document include geometric isomers, racemic mixtures,individual stereoisomers, and optically active mixtures. It will beappreciated by those skilled in the art that one isomer may be moreactive than the others. The structures disclosed in the presentdisclosure are drawn in only one geometric form for clarity, but areintended to represent all geometric forms of the molecule.

Combinations

In another embodiment of this invention, molecules of Formula One may beused in combination (such as, in a compositional mixture, or asimultaneous or sequential application) with one or more activeingredients.

In another embodiment of this invention, molecules of Formula One may beused in combination (such as, in a compositional mixture, or asimultaneous or sequential application) with one or more activeingredients each having a MoA that is the same as, similar to, but morelikely—different from, the MoA of the molecules of Formula One.

In another embodiment, molecules of Formula One may be used incombination (such as, in a compositional mixture, or a simultaneous orsequential application) with one or more molecules having acaricidal,algicidal, avicidal, bactericidal, fungicidal, herbicidal, insecticidal,molluscicidal, nematicidal, rodenticidal, and/or virucidal properties.

In another embodiment, the molecules of Formula One may be used incombination (such as, in a compositional mixture, or a simultaneous orsequential application) with one or more molecules that areantifeedants, bird repellents, chemosterilants, herbicide safeners,insect attractants, insect repellents, mammal repellents, matingdisrupters, plant activators, plant growth regulators, and/orsynergists.

In another embodiment, molecules of Formula One may also be used incombination (such as in a compositional mixture, or a simultaneous orsequential application) with one or more biopesticides.

In another embodiment, in a pesticidal composition combinations of amolecule of Formula One and an active ingredient may be used in a widevariety of weight ratios. For example, in a two component mixture, theweight ratio of a molecule of Formula One to an active ingredient, maybe from about 100:1 to about 1:100; in another example the weight ratiomay be about 50:1 to about 1:50; in another example the weight ratio maybe about 20:1 to about 1:20; in another example the weight ratio may beabout 10:1 to about 1:10; in another example the weight ratio may beabout 5:1 to 1:5; in another example the weight ratio may be about 3:1to about 1:3; in another example the weight ratio may be about 2:1 toabout 1:2; and in a final example the weight ratio may be about 1:1 (SeeTable B). However, in general, weight ratios less than about 10:1 toabout 1:10 are preferred. It is also preferred sometimes to use a threeor four component mixture comprising a molecule of Formula One and oneor more active ingredients.

TABLE B Weight Ratios Molecule of the Formula One:active ingredient100:1 to 1:100 50:1 to 1:50 20:1 to 1:20 10:1 to 1:10 5:1 to 1:5 3:1 to1:3 2:1 to 1:2 1:1

Weight ratios of a molecule of Formula One to an active ingredient mayalso be depicted as X:Y; wherein X is the parts by weight of a moleculeof Formula One and Y is the parts by weight of active ingredient. Thenumerical range of the parts by weight for X is 0<X≦100 and the parts byweight for Y is 0<Y≦100 and is shown graphically in TABLE C. By way ofnon-limiting example, the weight ratio of a molecule of Formula One toan active ingredient may be 20:1.

TABLE C active ingredient 100 X, Y X, Y X, Y (Y) Parts by weight 50 X, YX, Y X, Y X, Y X, Y 20 X, Y X, Y X, Y X, Y X, Y 15 X, Y X, Y X, Y X, YX, Y 10 X, Y X, Y 5 X, Y X, Y X, Y X, Y 3 X, Y X, Y X, Y X, Y X, Y X, YX, Y 2 X, Y X, Y X, Y X, Y X, Y 1 X, Y X, Y X, Y X, Y X, Y X, Y X, Y X,Y X, Y 1 2 3 5 10 15 20 50 100 molecule of Formula One (X) Parts byweight

Ranges of weight ratios of a molecule of Formula One to an activeingredient may be depicted as X₁:Y₁ to X₂:Y₂, wherein X and Y aredefined as above.

In one embodiment, the range of weight ratios may be X₁:Y₁ to X₂:Y₂,wherein X₁>Y₁ and X₂<Y₂. By way of non-limiting example, the range of aweight ratio of a molecule of Formula One to an active ingredient may bebetween 3:1 and 1:3, inclusive of the endpoints.

In another embodiment, the range of weight ratios may be X₁:Y₁ to X₂:Y₂,wherein X₁>Y₁ and X₂>Y₂. By way of non-limiting example, the range ofweight ratio of a molecule of Formula One to an active ingredient may bebetween 15:1 and 3:1, inclusive of the endpoints.

In another embodiment, the range of weight ratios may be X₁:Y₁ to X₂:Y₂,wherein X₁<Y₁ and X₂<Y₂. By way of non-limiting example, the range ofweight ratios of a molecule of Formula One to an active ingredient maybe between about 1:3 and about 1:20, inclusive of the endpoints.

Formulations

A pesticide is rarely suitable for application in its pure form. It isusually necessary to add other substances so that the pesticide may beused at the required concentration and in an appropriate form,permitting ease of application, handling, transportation, storage, andmaximum pesticide activity. Thus, pesticides are formulated into, forexample, baits, concentrated emulsions, dusts, emulsifiableconcentrates, fumigants, gels, granules, microencapsulations, seedtreatments, suspension concentrates, suspoemulsions, tablets, watersoluble liquids, water dispersible granules or dry flowables, wettablepowders, and ultra-low volume solutions.

Pesticides are applied most often as aqueous suspensions or emulsionsprepared from concentrated formulations of such pesticides. Suchwater-soluble, water-suspendable, or emulsifiable formulations areeither solids, usually known as wettable powders, or water dispersiblegranules, or liquids usually known as emulsifiable concentrates, oraqueous suspensions. Wettable powders, which may be compacted to formwater dispersible granules, comprise an intimate mixture of thepesticide, a carrier, and surfactants. The concentration of thepesticide is usually from about 10% to about 90% by weight. The carrieris usually selected from among the attapulgite clays, themontmorillonite clays, the diatomaceous earths, or the purifiedsilicates. Effective surfactants, comprising from about 0.5% to about10% of the wettable powder, are found among sulfonated lignins,condensed naphthalenesulfonates, naphthalenesulfonates,alkylbenzenesulfonates, alkyl sulfates, and non-ionic surfactants suchas ethylene oxide adducts of alkyl phenols.

Emulsifiable concentrates of pesticides comprise a convenientconcentration of a pesticide, such as from about 50 to about 500 gramsper liter of liquid dissolved in a carrier that is either a watermiscible solvent or a mixture of water-immiscible organic solvent andemulsifiers. Useful organic solvents include aromatics, especiallyxylenes and petroleum fractions, especially the high-boilingnaphthalenic and olefinic portions of petroleum such as heavy aromaticnaphtha. Other organic solvents may also be used, such as the terpenicsolvents including rosin derivatives, aliphatic ketones such ascyclohexanone, and complex alcohols such as 2-ethoxyethanol. Suitableemulsifiers for emulsifiable concentrates are selected from conventionalanionic and non-ionic surfactants.

Aqueous suspensions comprise suspensions of water-insoluble pesticidesdispersed in an aqueous carrier at a concentration in the range fromabout 5% to about 50% by weight. Suspensions are prepared by finelygrinding the pesticide and vigorously mixing it into a carrier comprisedof water and surfactants. Ingredients, such as inorganic salts andsynthetic or natural gums may also be added, to increase the density andviscosity of the aqueous carrier. It is often most effective to grindand mix the pesticide at the same time by preparing the aqueous mixtureand homogenizing it in an implement such as a sand mill, ball mill, orpiston-type homogenizer.

Pesticides may also be applied as granular compositions that areparticularly useful for applications to the soil. Granular compositionsusually contain from about 0.5% to about 10% by weight of the pesticide,dispersed in a carrier that comprises clay or a similar substance. Suchcompositions are usually prepared by dissolving the pesticide in asuitable solvent and applying it to a granular carrier which has beenpre-formed to the appropriate particle size, in the range of from about0.5 to about 3 mm. Such compositions may also be formulated by making adough or paste of the carrier and molecule and crushing and drying toobtain the desired granular particle size.

Dusts containing a pesticide are prepared by intimately mixing thepesticide in powdered form with a suitable dusty agricultural carrier,such as kaolin clay, ground volcanic rock, and the like. Dusts cansuitably contain from about 1% to about 10% of the pesticide. Dusts maybe applied as a seed dressing or as a foliage application with a dustblower machine.

It is equally practical to apply a pesticide in the form of a solutionin an appropriate organic solvent, usually petroleum oil, such as thespray oils, which are widely used in agricultural chemistry.

Pesticides can also be applied in the form of an aerosol composition. Insuch compositions the pesticide is dissolved or dispersed in a carrier,which is a pressure-generating propellant mixture. The aerosolcomposition is packaged in a container from which the mixture isdispensed through an atomizing valve.

Pesticide baits are formed when the pesticide is mixed with food or anattractant or both. When the pests eat the bait they also consume thepesticide. Baits may take the form of granules, gels, flowable powders,liquids, or solids. Baits may be used in pest harborages.

Fumigants are pesticides that have a relatively high vapor pressure andhence can exist as a gas in sufficient concentrations to kill pests insoil or enclosed spaces. The toxicity of the fumigant is proportional toits concentration and the exposure time. They are characterized by agood capacity for diffusion and act by penetrating the pest'srespiratory system or being absorbed through the pest's cuticle.Fumigants are applied to control stored product pests under gas proofsheets, in gas sealed rooms or buildings or in special chambers.

Pesticides may be microencapsulated by suspending the pesticideparticles or droplets in plastic polymers of various types. By alteringthe chemistry of the polymer or by changing factors in the processing,microcapsules may be formed of various sizes, solubility, wallthicknesses, and degrees of penetrability. These factors govern thespeed with which the active ingredient within is released, which inturn, affects the residual performance, speed of action, and odor of theproduct.

Oil solution concentrates are made by dissolving pesticide in a solventthat will hold the pesticide in solution. Oil solutions of a pesticideusually provide faster knockdown and kill of pests than otherformulations due to the solvents themselves having pesticidal action andthe dissolution of the waxy covering of the integument increasing thespeed of uptake of the pesticide. Other advantages of oil solutionsinclude better storage stability, better penetration of crevices, andbetter adhesion to greasy surfaces.

Another embodiment is an oil-in-water emulsion, wherein the emulsioncomprises oily globules which are each provided with a lamellar liquidcrystal coating and are dispersed in an aqueous phase, wherein each oilyglobule comprises at least one molecule which is agriculturally active,and is individually coated with a monolamellar or oligolamellar layercomprising: (1) at least one non-ionic lipophilic surface-active agent,(2) at least one non-ionic hydrophilic surface-active agent and (3) atleast one ionic surface-active agent, wherein the globules having a meanparticle diameter of less than 800 nanometers.

Other Formulation Components

Generally, when the molecules disclosed in Formula One are used in aformulation, such formulation can also contain other components. Thesecomponents include, but are not limited to, (this is a non-exhaustiveand non-mutually exclusive list) wetters, spreaders, stickers,penetrants, buffers, sequestering agents, drift reduction agents,compatibility agents, anti-foam agents, cleaning agents, andemulsifiers. A few components are described forthwith.

A wetting agent is a substance that when added to a liquid increases thespreading or penetration power of the liquid by reducing the interfacialtension between the liquid and the surface on which it is spreading.Wetting agents are used for two main functions in agrochemicalformulations: during processing and manufacture to increase the rate ofwetting of powders in water to make concentrates for soluble liquids orsuspension concentrates; and during mixing of a product with water in aspray tank to reduce the wetting time of wettable powders and to improvethe penetration of water into water-dispersible granules. Examples ofwetting agents used in wettable powder, suspension concentrate, andwater-dispersible granule formulations are: sodium lauryl sulfate;sodium dioctyl sulfosuccinate; alkyl phenol ethoxylates; and aliphaticalcohol ethoxylates.

A dispersing agent is a substance which adsorbs onto the surface ofparticles and helps to preserve the state of dispersion of the particlesand prevents them from reaggregating. Dispersing agents are added toagrochemical formulations to facilitate dispersion and suspension duringmanufacture, and to ensure the particles redisperse into water in aspray tank. They are widely used in wettable powders, suspensionconcentrates and water-dispersible granules. Surfactants that are usedas dispersing agents have the ability to adsorb strongly onto a particlesurface and provide a charged or steric barrier to reaggregation ofparticles. The most commonly used surfactants are anionic, non-ionic, ormixtures of the two types. For wettable powder formulations, the mostcommon dispersing agents are sodium lignosulfonates. For suspensionconcentrates, very good adsorption and stabilization are obtained usingpolyelectrolytes, such as sodium naphthalene sulfonate formaldehydecondensates.

Tristyrylphenol ethoxylate phosphate esters are also used. Non-ionicssuch as alkylarylethylene oxide condensates and EO-PO block copolymersare sometimes combined with anionics as dispersing agents for suspensionconcentrates. In recent years, new types of very high molecular weightpolymeric surfactants have been developed as dispersing agents. Thesehave very long hydrophobic ‘backbones’ and a large number of ethyleneoxide chains forming the ‘teeth’ of a ‘comb’ surfactant. These highmolecular weight polymers can give very good long-term stability tosuspension concentrates because the hydrophobic backbones have manyanchoring points onto the particle surfaces. Examples of dispersingagents used in agrochemical formulations are: sodium lignosulfonates;sodium naphthalene sulfonate formaldehyde condensates; tristyrylphenolethoxylate phosphate esters; aliphatic alcohol ethoxylates; alkylethoxylates; EO-PO block copolymers; and graft copolymers.

An emulsifying agent is a substance which stabilizes a suspension ofdroplets of one liquid phase in another liquid phase. Without theemulsifying agent the two liquids would separate into two immiscibleliquid phases. The most commonly used emulsifier blends containalkylphenol or aliphatic alcohol with twelve or more ethylene oxideunits and the oil-soluble calcium salt of dodecylbenzenesulfonic acid. Arange of hydrophile-lipophile balance (“HLB”) values from 8 to 18 willnormally provide good stable emulsions. Emulsion stability can sometimesbe improved by the addition of a small amount of an EO-PO blockcopolymer surfactant.

A solubilizing agent is a surfactant which will form micelles in waterat concentrations above the critical micelle concentration. The micellesare then able to dissolve or solubilize water-insoluble materials insidethe hydrophobic part of the micelle. The types of surfactants usuallyused for solubilization are non-ionics, sorbitan monooleates, sorbitanmonooleate ethoxylates, and methyl oleate esters.

Surfactants are sometimes used, either alone or with other additivessuch as mineral or vegetable oils as adjuvants to spray-tank mixes toimprove the biological performance of the pesticide on the target. Thetypes of surfactants used for bioenhancement depend generally on thenature and mode of action of the pesticide. However, they are oftennon-ionics such as: alkyl ethoxylates; linear aliphatic alcoholethoxylates; aliphatic amine ethoxylates.

A carrier or diluent in an agricultural formulation is a material addedto the pesticide to give a product of the required strength. Carriersare usually materials with high absorptive capacities, while diluentsare usually materials with low absorptive capacities. Carriers anddiluents are used in the formulation of dusts, wettable powders,granules and water-dispersible granules.

Organic solvents are used mainly in the formulation of emulsifiableconcentrates, oil-in-water emulsions, suspoemulsions, and ultra-lowvolume formulations, and to a lesser extent, granular formulations.Sometimes mixtures of solvents are used. The first main groups ofsolvents are aliphatic paraffinic oils such as kerosene or refinedparaffins. The second main group (and the most common) comprises thearomatic solvents such as xylene and higher molecular weight fractionsof C9 and C10 aromatic solvents. Chlorinated hydrocarbons are useful ascosolvents to prevent crystallization of pesticides when the formulationis emulsified into water. Alcohols are sometimes used as cosolvents toincrease solvent power. Other solvents may include vegetable oils, seedoils, and esters of vegetable and seed oils.

Thickeners or gelling agents are used mainly in the formulation ofsuspension concentrates, emulsions and suspoemulsions to modify therheology or flow properties of the liquid and to prevent separation andsettling of the dispersed particles or droplets. Thickening, gelling,and anti-settling agents generally fall into two categories, namelywater-insoluble particulates and water-soluble polymers. It is possibleto produce suspension concentrate formulations using clays and silicas.Examples of these types of materials, include, but are not limited to,montmorillonite, bentonite, magnesium aluminum silicate, andattapulgite. Water-soluble polysaccharides have been used asthickening-gelling agents for many years. The types of polysaccharidesmost commonly used are natural extracts of seeds and seaweeds or aresynthetic derivatives of cellulose. Examples of these types of materialsinclude, but are not limited to, guar gum; locust bean gum; carrageenam;alginates; methyl cellulose; sodium carboxymethyl cellulose (SCMC);hydroxyethyl cellulose (HEC). Other types of anti-settling agents arebased on modified starches, polyacrylates, polyvinyl alcohol andpolyethylene oxide. Another good anti-settling agent is xanthan gum.

Microorganisms can cause spoilage of formulated products. Thereforepreservation agents are used to eliminate or reduce their effect.Examples of such agents include, but are not limited to: propionic acidand its sodium salt; sorbic acid and its sodium or potassium salts;benzoic acid and its sodium salt; p-hydroxybenzoic acid sodium salt;methyl p-hydroxybenzoate; and 1,2-benzisothiazolin-3-one (BIT).

The presence of surfactants often causes water-based formulations tofoam during mixing operations in production and in application through aspray tank. In order to reduce the tendency to foam, anti-foam agentsare often added either during the production stage or before fillinginto bottles. Generally, there are two types of anti-foam agents, namelysilicones and non-silicones. Silicones are usually aqueous emulsions ofdimethyl polysiloxane, while the non-silicone anti-foam agents arewater-insoluble oils, such as octanol and nonanol, or silica. In bothcases, the function of the anti-foam agent is to displace the surfactantfrom the air-water interface.

“Green” agents (e.g., adjuvants, surfactants, solvents) can reduce theoverall environmental footprint of crop protection formulations. Greenagents are biodegradable and generally derived from natural and/orsustainable sources, e.g. plant and animal sources. Specific examplesare: vegetable oils, seed oils, and esters thereof, also alkoxylatedalkyl polyglucosides.

Applications

Molecules of Formula One may be applied to any locus. Particular croploci to apply such molecules include loci where alfalfa, almonds,apples, barley, beans, canola, corn, cotton, crucifers, lettuce, oats,oranges, pears, peppers, potatoes, rice, sorghum, soybeans,strawberries, sugarcane, sugar beets, sunflowers, tobacco, tomatoes,wheat, and other valuable crops are growing or the seeds thereof aregoing to be planted.

Molecules of Formula One may also be applied where plants, such ascrops, are growing and where there are low levels (even no actualpresence) of pests that can commercially damage such plants. Applyingsuch molecules in such locus is to benefit the plants being grown insuch locus. Such benefits, may include, but are not limited to: helpingthe plant grow a better root system; helping the plant better withstandstressful growing conditions; improving the health of a plant; improvingthe yield of a plant (e.g. increased biomass and/or increased content ofvaluable ingredients); improving the vigor of a plant (e.g. improvedplant growth and/or greener leaves); improving the quality of a plant(e.g. improved content or composition of certain ingredients); andimproving the tolerance to abiotic and/or biotic stress of the plant.

Molecules of Formula One may be applied with ammonium sulfate whengrowing various plants as this may provide additional benefits.

Molecules of Formula One may be applied on, in, or around plantsgenetically modified to express specialized traits, such as Bacillusthuringiensis or other insecticidal toxins, or those expressingherbicide resistance, or those with “stacked” foreign genes expressinginsecticidal toxins, herbicide resistance, nutrition-enhancement, or anyother beneficial traits.

Molecule of Formula One may be applied to the foliar and/or fruitingportions of plants to control pests. Such molecules will either come indirect contact with the pest, or the pest will consume such moleculeswhen eating the plant or while extracting sap from the plant.

Molecule of Formula One may also be applied to the soil, and whenapplied in this manner, root and stem feeding pests may be controlled.The roots may absorb such molecules thereby taking it up into the foliarportions of the plant to control above ground chewing and sap feedingpests.

Systemic movement of pesticides in plants may be utilized to controlpests on one portion of the plant by applying (for example by spraying alocus) a molecule of Formula One to a different portion of the plant.For example, control of foliar-feeding insects may be achieved by dripirrigation or furrow application, by treating the soil with for examplepre- or post-planting soil drench, or by treating the seeds of a plantbefore planting.

Molecules of Formula One may be used with baits. Generally, with baits,the baits are placed in the ground where, for example, termites can comeinto contact with, and/or be attracted to, the bait. Baits can also beapplied to a surface of a building, (horizontal, vertical, or slantsurface) where, for example, ants, termites, cockroaches, and flies, cancome into contact with, and/or be attracted to, the bait.

Molecules of Formula One may be encapsulated inside, or placed on thesurface of a capsule. The size of the capsules can range from nanometersize (about 100-900 nanometers in diameter) to micrometer size (about10-900 microns in diameter).

Molecules of Formula One may be applied to eggs of pests. Because of theunique ability of the eggs of some pests to resist certain pesticides,repeated applications of such molecules may be desirable to controlnewly emerged larvae.

Molecules of Formula One may be applied as seed treatments. Seedtreatment may be applied to all types of seeds, including those fromwhich plants genetically modified to express specialized traits willgerminate. Representative examples include those expressing proteinstoxic to invertebrate pests, such as Bacillus thuringiensis or otherinsecticidal toxins, those expressing herbicide resistance, such as“Roundup Ready” seed, or those with “stacked” foreign genes expressinginsecticidal toxins, herbicide resistance, nutrition-enhancement,drought resistance, or any other beneficial traits. Furthermore, suchseed treatments with molecules of Formula One may further enhance theability of a plant to better withstand stressful growing conditions.This results in a healthier, more vigorous plant, which can lead tohigher yields at harvest time. Generally, about 1 gram of such moleculesto about 500 grams per 100,000 seeds is expected to provide goodbenefits, amounts from about 10 grams to about 100 grams per 100,000seeds is expected to provide better benefits, and amounts from about 25grams to about 75 grams per 100,000 seeds is expected to provide evenbetter benefits.

Molecules of Formula One may be applied with one or more activeingredients in a soil amendment.

Molecules of Formula One may be used for controlling endoparasites andectoparasites in the veterinary medicine sector or in the field ofnon-human-animal keeping. Such molecules may be applied by oraladministration in the form of, for example, tablets, capsules, drinks,granules, by dermal application in the form of, for example, dipping,spraying, pouring on, spotting on, and dusting, and by parenteraladministration in the form of, for example, an injection.

Molecules of Formula One may also be employed advantageously inlivestock keeping, for example, cattle, sheep, pigs, chickens, salmon,and geese. They may also be employed advantageously in pets such as,horses, dogs, and cats. Particular pests to control would be fleas andticks that are bothersome to such animals. Suitable formulations areadministered orally to the animals with the drinking water or feed. Thedosages and formulations that are suitable depend on the species.

Molecules of Formula One may also be used for controlling parasiticworms, especially of the intestine, in the animals listed above.

Molecules of Formula One may also be employed in therapeutic methods forhuman health care. Such methods include, but are limited to, oraladministration in the form of, for example, tablets, capsules, drinks,granules, and by dermal application.

Molecules of Formula One may also be applied to invasive pests.

Pests around the world have been migrating to new environments (for suchpest) and thereafter becoming a new invasive species in such newenvironment. Such molecules may also be used on such new invasivespecies to control them in such new environments.

Consequently, in light of the above and the Tables in the Table Section,the following items are provided.

1. A molecule having the following formula

wherein:

-   -   (A) R¹, R⁵, R⁶, R¹¹, and R¹² are each independently selected        from the group consisting of H, F, Cl, Br, I, CN, (C₁-C₆)alkyl,        (C₁-C₆)haloalkyl, (C₁-C₆)alkoxy, and (C₁-C₄)haloalkoxy    -   preferably, R¹, R⁵, R⁶, R¹¹, and R¹² are H;    -   (B) R², R³, and R⁴ are each independently selected from the        group consisting of H, F, Cl, Br, I, CN, (C₁-C₆)alkyl,        (C₂-C₆)alkenyl, (C₂-C₆)alkynyl, (C₁-C₆)haloalkyl, (C₁-C₆)alkoxy,        and (C₁-C₆)haloalkoxy    -   preferably, R², R³, and R⁴ are H, F, Cl, Br, CH₃, or CH═CH₂;    -   (C) R⁷ is (C₁-C₆)haloalkyl    -   preferably R⁷ is CF₃, CF₂CH₃, or CF₂CH₂CH₃;    -   (D) R⁹ is selected from the group consisting of (F), H, F, Cl,        Br, I, CN, (C₁-C₄)alkyl, (C₁-C₄)haloalkyl, (C₁-C₄)alkoxy, and        (C₁-C₄)haloalkoxy    -   preferably R⁹ is H;    -   (E) R¹⁰ is selected from the group consisting of (F), F, Cl, Br,        I, CN, (C₁-C₆)alkyl, (C₂-C₆)alkenyl, (C₂-C₆)alkynyl,        (C₁-C₆)haloalkyl, (C₁-C₆)alkoxy, and (C₁-C₆)haloalkoxy    -   preferably R¹⁰ is Cl, Br, I, CH₃, or CF₃;    -   (F) R⁹ and R¹⁰ together can optionally form a 3- to 5-membered        saturated or unsaturated, hydrocarbyl link,    -   wherein said hydrocarbyl link may optionally be substituted with        one or more substituents independently selected from the group        consisting of F, Cl, Br, I, CN, OH, and oxo;    -   (G) Q¹ and Q² are each independently O or S    -   preferably Q¹ and Q² are O;    -   (H) R¹³ is selected from the group consisting of H,        (C₁-C₆)alkyl, (C₂-C₆)alkenyl, (C₁-C₆)haloalkyl, (C₁-C₆)alkoxy,        and (C₁-C₆)haloalkoxy    -   preferably R¹³ is CH₃ or CH₂CH₃;    -   (I) R¹⁴ is selected from the group consisting of (K), (O), H,        (C₁-C₄)alkyl, (C₂-C₆)alkenyl, (C₁-C₆)haloalkyl, (C₁-C₆)alkoxy,        and (C₁-C₆)haloalkoxy    -   preferably R¹⁴ is CH₃ or CH₂CH₃;    -   (J) R¹⁵ is selected from the group consisting of (K), H,        (C₁-C₆)alkyl, (C₂-C₆)alkenyl, (C₁-C₆)haloalkyl, (C₁-C₆)alkoxy,        and (C₁-C₆)haloalkoxy    -   preferably R¹⁵ is CH₃ or CH₂CH₃;    -   (K) R¹⁴ and R¹⁵ together can optionally form a 2- to 5-membered        saturated, hydrocarbyl link,        -   wherein said hydrocarbyl link may optionally be substituted            with one or more substituents independently selected from            the group consisting of F, Cl, Br, I, and CN    -   preferably R¹⁴ and R¹⁵ together form a 2-membered saturated,        hydrocarbyl link;    -   (L) L is selected from the group consisting of        -   (1) a bond, and        -   (2) a (C₁-C₆)alkyl wherein said alkyl is optionally            substituted with one or more substituents independently            selected from the group consisting of F, Cl, CN, OH, and            oxo;    -   preferably L is a bond;    -   (M) X is selected from the group consisting of        -   (1) R¹⁷, and        -   (2) a NR¹⁶R¹⁷,        -   (3) OR¹⁷, and        -   (4) SR¹⁷;    -   preferably X is a bond or NR¹⁶R¹⁷;    -   (N) R¹⁶ is selected from the group consisting of (O), (Q), H,        (C₁-C₆)alkyl, (C₂-C₆)alkenyl, (C₁-C₆)haloalkyl, (C₁-C₆)alkoxy,        (C₂-C₆)alkenyloxy, (C₁-C₆)haloalkoxy, amino, and        NHC(O)O(C₁-C₆)alkyl    -   preferably R¹⁶ is CH₃, CH₂CH₃, OCH₃, OCH₂CH═CH₂, NH₂, or        NHC(O)OC(CH₃)₃;    -   (O) R¹⁴ and R¹⁶ together can optionally form a 2- to 4-membered        saturated link that is either (1) a hydrocarbyl link or (2) a        heterohydrocarbyl link that contains one or more heteroatoms        selected from the group consisting of nitrogen, sulfur, and        oxygen,        -   wherein said link may optionally be substituted with one or            more substituents independently selected from the group            consisting of F, Cl, Br, I, CN, OH, and oxo    -   preferably R¹⁴ and R¹⁶ together form a 2- to 4-membered        saturated link that is either (1) a hydrocarbyl link or (2) a        heterohydrocarbyl link that contains one or more oxygen atoms;    -   (P) R¹⁷ is selected from the group consisting of (Q), H,        (C₁-C₆)alkyl, (C₂-C₆)alkenyl, (C₂-C₆)alkynyl, (C₁-C₆)haloalkyl,        (C₂-C₆)haloalkenyl, (C₃-C₆)halocycloalkyl, (C₁-C₆)alkoxy,        (C₃-C₆)cycloalkyl, (C₂-C₆)alkenyloxy, (C₁-C₆)haloalkoxy, and        (C₁-C₆)alkyl(C₃-C₆)cycloalkyl    -   preferably R¹⁷ is CH₂CH₃, CH₂CH₂CH₂CH₃, CH₂CH₂CH(CH₃)₂,        CH₂CH═CH₂, CH₂C≡CH, CH₂CHF₂, CH₂CF₃, CH₂CH₂CF₃, CH₂CF₂CH₃,        CH(CH₃)CF₃, CH₂CH₂CH₂CF₃, CH═CHCH₂CF₃, 3,3-difluorocyclobutyl,        CH₂CH₂cyclopropyl, or CH₂cyclobutyl;    -   (Q) R¹⁶ and R¹⁷ together can optionally form a 2- to 6-membered        saturated link that is either (1) a hydrocarbyl link or (2) a        heterohydrocarbyl link that contains one or more heteroatoms        selected from the group consisting of nitrogen, sulfur, and        oxygen,    -   wherein said link may optionally be substituted with one or more        substituents independently selected from the group consisting of        F, Cl, Br, I, CN, OH, and oxo; and    -   agriculturally acceptable acid addition salts, salt derivatives,        solvates, ester derivatives, crystal polymorphs, isotopes,        resolved stereoisomers, and tautomers, of the molecules of        Formula One.        2. A molecule according to 1 wherein    -   (A) R¹, R⁵, R⁶, R¹¹, and R¹² are H;    -   (B) R², R³, and R⁴ are each independently selected from the        group consisting of H, F, Cl, Br, (C₁-C₆)alkyl, and        (C₂-C₆)alkenyl;    -   (C) R⁷ is (C₁-C₆)haloalkyl;    -   (D) R⁹ is H;    -   (E) R¹⁰ is selected from the group consisting of Cl, Br, I,        (C₁-C₆)alkyl, and (C₁-C₆)haloalkyl;    -   (G) Q¹ and Q² are O;    -   (H) R¹³ is selected from the group consisting of H and        (C₁-C₆)alkyl;    -   (I) R¹⁴ is selected from the group consisting of (K), (O), H,        and (C₁-C₄)alkyl;    -   (J) R¹⁵ is selected from the group consisting of (K), H, and        (C₁-C₆)alkyl;    -   (K) R¹⁴ and R¹⁵ together can optionally form a 2- to 5-membered        saturated, hydrocarbyl link;    -   (L) L is a bond;    -   (M) X is selected from the group consisting of        -   (1) R¹⁷, and        -   (2) a NR¹⁶R¹⁷;    -   (N) R¹⁶ is selected from the group consisting of (O), H,        (C₁-C₆)alkyl, (C₁-C₆)alkoxy, (C₂-C₆)alkenyloxy, amino, and        NHC(O)O(C₁-C₆)alkyl;    -   (O) R¹⁴ and R¹⁶ together can optionally form a 2- to 4-membered        saturated link that is either (1) a hydrocarbyl link or (2) a        heterohydrocarbyl link that contains one or more oxygen atoms;    -   (P) R¹⁷ is selected from the group consisting of H,        (C₁-C₆)alkyl, (C₂-C₆)alkenyl, (C₂-C₆)alkynyl, (C₁-C₆)haloalkyl,        (C₂-C₆)haloalkenyl, (C₃-C₆)halocycloalkyl, and        (C₁-C₆)alkyl(C₃-C₆)cycloalkyl.        3. A molecule according to 1 wherein said molecule is selected        from one of the molecules in Table 2.        4. A molecule according to 1 wherein said molecule is selected        from one of the molecules in Table 1.        5. A pesticidal composition comprising a molecule according to        any one of 1, 2, 3, or 4, further comprising one or more active        ingredients.        6. A pesticidal composition according to 5 wherein said active        ingredient is from AIGA.        7. A pesticidal composition according to 5 wherein said active        ingredient is selected from the group consisting of AI-1,        1,3-dichloropropene, chlorpyrifos, chlorpyrifos-methyl,        hexaflumuron, methoxyfenozide, noviflumuron, spinetoram,        spinosad, sulfoxaflor, and sulfuryl fluoride.        8. A pesticidal composition comprising a molecule according to        any one of 1, 2, 3, or 4, further comprising a MoA Material.        9. A pesticidal composition according to 7 wherein said MoA        Material is from MoAMGA.        10. A pesticidal composition according to any one of 5, 6, 7, 8,        or 9, wherein the weight ratio of the molecule according to        Formula One to said active ingredient is    -   (a) 100:1 to 1:100;    -   (b) 50:1 to 1:50;    -   (c) 20:1 to 1:20;    -   (d) 10:1 to 1:10;    -   (e) 5:1 to 1:5;    -   (f) 3:1 to 1:3;    -   (g) 2:1 to 1:2; or    -   (h) 1:1.        11. A process to control a pest said process comprising applying        to a locus, a pesticidally effective amount of a molecule        according to any one of the 1, 2, 3, or 4.        12. A process to control a pest said process comprising applying        to a locus, a pesticidally effective amount of a pesticidal        composition according to any one of the 5, 6, 7, 8, 9, or 10.        13. A molecule according to any one of 1, 2, 3, or 4, or a        pesticidal composition according to any of 5, 6, 7, 8, 9, or 10,        wherein said molecule is in the form of agriculturally        acceptable acid addition salt.        14. A molecule according to any one of 1, 2, 3, or 4, or a        pesticidal composition according to any of 5, 6, 7, 8, 9, or 10,        wherein said molecule is in the form of a salt derivative.        15. A molecule according to any one of 1, 2, 3, or 4, or a        pesticidal composition according to any of 5, 6, 7, 8, 9, or 10,        wherein said molecule is in the form of solvate.        16. A molecule according to any one of 1, 2, 3, or 4, or a        pesticidal composition according to any of 5, 6, 7, 8, 9, or 10,        wherein said molecule is in the form of an ester derivative.        17. A molecule according to any one of 1, 2, 3, or 4, or a        pesticidal composition according to any of 5, 6, 7, 8, 9, or 10,        wherein said molecule is in the form of a crystal polymorph.        18. A molecule according to any one of 1, 2, 3, or 4, or a        pesticidal composition according to any of 5, 6, 7, 8, 9, or 10,        wherein said molecule has deuterium, tritium, and or ¹⁴C.        19. A molecule according to any one of 1, 2, 3, or 4, or a        pesticidal composition according to any of 5, 6, 7, 8, 9, or 10,        wherein said molecule is in the form of one or more        stereoisomers.        20. A molecule according to any one of 1, 2, 3, or 4, or a        pesticidal composition according to any of 5, 6, 7, 8, 9, or 10,        wherein said molecule is in the form of a resolved stereoisomer.        21. A pesticidal composition according to any of 5, 6, 7, 8, 9,        or 10, wherein said pesticidal composition further comprises        another active ingredient.        22. A pesticidal composition according to any of 5, 6, 7, 8, 9,        or 10, wherein said pesticidal composition further comprises two        more active ingredients.        23. A pesticidal composition according to any of 5, 6, 7, 8, 9,        or 10, wherein said active ingredient has a MOA different from        the MoA of said molecule of Formula One.        24. A pesticidal composition according to any of 5, 6, 7, 8, 9,        or 10, wherein said pesticidal composition comprises an active        ingredient having acaricidal, algicidal, avicidal, bactericidal,        fungicidal, herbicidal, insecticidal, molluscicidal,        nematicidal, rodenticidal, and/or virucidal properties.        25. A pesticidal composition according to any of 5, 6, 7, 8, 9,        or 10, wherein said pesticidal composition comprises an active        ingredient that is an antifeedant, bird repellent,        chemosterilant, herbicide safener, insect attractant, insect        repellent, mammal repellent, mating disrupter, plant activator,        plant growth regulator, and/or synergist.        26. A pesticidal composition according to any of 5, 6, 7, 8, 9,        or 10, wherein said pesticidal composition comprises an active        ingredient that is a biopesticide.        27. A pesticidal composition according to any of 5, 6, 7, 8, 9,        or 10, wherein said weight ratio of a molecule of Formula One to        an active ingredient is 100:1 to 1:100.        28. A pesticidal composition according to any of 5, 6, 7, 8, 9,        or 10, wherein said weight ratio of a molecule of Formula One to        an active ingredient is 50:1 to 1:50.        29. A pesticidal composition according to any of 5, 6, 7, 8, 9,        or 10, wherein said weight ratio of a molecule of Formula One to        an active ingredient is 20:1 to 1:20.        30. A pesticidal composition according to any of 5, 6, 7, 8, 9,        or 10, wherein said weight ratio of a molecule of Formula One to        an active ingredient is 10:1 to 1:10.        31. A pesticidal composition according to any of 5, 6, 7, 8, 9,        or 10, wherein said weight ratio of a molecule of Formula One to        an active ingredient is 5:1 to 1:5.        32. A pesticidal composition according to any of 5, 6, 7, 8, 9,        or 10, wherein said weight ratio of a molecule of Formula One to        an active ingredient is 3:1 to 1:3.        33. A pesticidal composition according to any of 5, 6, 7, 8, 9,        or 10, wherein said weight ratio of a molecule of Formula One to        an active ingredient is 2:1 to 1:2.        34. A pesticidal composition according to any of 5, 6, 7, 8, 9,        or 10, wherein said weight ratio of a molecule of Formula One to        an active ingredient is 1:1        35. A pesticidal composition according to any of 5, 6, 7, 8, 9,        or 10, wherein said weight ratio of a molecule of Formula One to        an active ingredient is depicted as X:Y; wherein X is the parts        by weight of a molecule of Formula One and Y is the parts by        weight of active ingredient; further wherein the numerical range        of the parts by weight for X is 0<X≦100 and the parts by weight        for Y is 0<Y≦100; and further wherein X and Y are selected from        Table C

TABLE C active ingredient 100 X, Y X, Y X, Y (Y) Parts by weight 50 X, YX, Y X, Y X, Y X, Y 20 X, Y X, Y X, Y X, Y X, Y 15 X, Y X, Y X, Y X, YX, Y 10 X, Y X, Y 5 X, Y X, Y X, Y X, Y 3 X, Y X, Y X, Y X, Y X, Y X, YX, Y 2 X, Y X, Y X, Y X, Y X, Y 1 X, Y X, Y X, Y X, Y X, Y X, Y X, Y X,Y X, Y 1 2 3 5 10 15 20 50 100 molecule of Formula One (X) Parts byweight36. A pesticidal composition according to 35 wherein a range of weightratios of a molecule of Formula One to an active ingredient is depictedas X₁:Y₁ to X₂:Y₂; further wherein X₁>Y₁ and X₂<Y₂.37. A pesticidal composition according to 35 wherein a range of weightratios of a molecule of Formula One to an active ingredient is depictedas X₁:Y₁ to X₂:Y₂; further wherein X₁>Y₁ and X₂>Y₂.38. A pesticidal composition according to 35 wherein a range of weightratios of a molecule of Formula One to an active ingredient is depictedas X₁:Y₁ to X₂:Y₂; further wherein X₁<Y₁ and X₂<Y₂.39. A pesticidal composition according to 35 wherein said composition issynergistic.40. A process according to 12 wherein said pest is from PhylumArthropoda.41. A process according to 12 wherein said pest is from Phylum Mollusca.42. A process according to 12 wherein said pest is from Phylum Nematoda.43. A process according to 12 wherein said pests are are ants, aphids,beetles, bristletails, cockroaches, crickets, earwigs, fleas, flies,grasshoppers, leafhoppers, lice (including sea lice), locusts, mites,moths, nematodes, scales, symphylans, termites, thrips, ticks, wasps,and/or whiteflies.44. A process according to 12 wherein said locus is where alfalfa,almonds, apples, barley, beans, canola, corn, cotton, crucifers,lettuce, oats, oranges, pears, peppers, potatoes, rice, sorghum,soybeans, strawberries, sugarcane, sugar beets, sunflowers, tobacco,tomatoes, wheat, and other valuable crops are growing or the seedsthereof are planted.45. A pesticidal composition according to any of 5, 6, 7, 8, 9, or 10,wherein said pesticidal composition further comprises ammonium sulfate.46. A process according to 12 wherein said locus is where plantsgenetically modified to express specialized traits are planted.47. A process according to 12 wherein said applying is done to thefoliar and/or fruiting portions of plants.48. A process according to 12 wherein said applying is done to the soil.49. A process according to 12 wherein said applying is done by dripirrigation, furrow application, or pre- or post-planting soil drench.50. A process according to 12 wherein said applying is done to thefoliar and/or fruiting portions of plants, or by treating the seeds of aplant before planting.51. A pesticidal composition comprising a molecule according to any oneof 1, 2, 3, or 4, and a seed.52. A process comprising applying a molecule according to any one of 1,2, 3, or 4, or a pesticidal composition according to any of 5, 6, 7, 8,9, or 10, to a seed.53. A process comprising applying a molecule according to 1, 2, 3, or 4,to a locus that includes a non-human animal to control endoparasitesand/or ectoparasites.54. A process to produce a pesticidal composition, said processcomprising mixing a molecule according to any one of claims 1, 2, 3, or4, with one or more active ingredients.

The headings in this document are for convenience only and must not beused to interpret any portion hereof.

Table Section

TABLE 2 Structure and Preparation Method for F Series Molecules No.Structure Prep.* F1 

13 F2 

13 F3 

13, 15 F4 

14 F5 

14 F6 

13 F7 

13 F8 

15 F9 

14 F10 

14 F11 

13 F12 

13 F13 

13 F14 

13 F15 

13 F16 

13 F17 

17 F18 

13 F19 

13 F20 

13 F21 

15 F22 

13 F23 

13 F24 

15 F25 

13 F26 

13 F27 

15 F28 

15 F29 

13 F30 

13 F31 

13 F32 

13 F33 

13 F34 

16 F35 

13 F36 

13 F37 

16 F38 

13 F39 

13 F40 

13 F41 

13 F42 

13 F43 

13 F44 

16 F45 

16 F46 

16 F47 

13 F48 

13 F49 

13 F50 

13 F51 

13 F52 

16 F53 

13 F54 

15 F55 

15 F56 

13 F57 

18 F58 

13 F59 

16 F60 

16 F61 

16 F62 

13 F63 

13 F64 

13 F65 

13 F66 

13 F67 

13 F68 

15 F69 

16 F70 

16 F71 

16 F72 

16 F73 

16 F74 

16 F75 

16 F76 

16 F77 

16 F78 

16 F79 

13 F80 

16 F81 

13 F82 

13 F83 

13 F84 

13 F85 

16 F86 

16 F87 

13 F88 

13 F89 

14 F90 

14 F91 

14 F92 

14 F93 

14 F94 

14 F95 

14 F96 

13 F97 

13 F98 

13 F99 

15 F100

13 F101

14 F102

16 F103

16 F104

15 F105

16 F106

13 F107

13 F108

16 F109

16 F110

16 F111

16 F112

13 F113

16 F114

16 F115

16 F116

16 F117

16 F118

16 F119

16 F120

16 F121

16 F122

16 F123

13 F124

13 F125

13 F126

15 F127

15 F128

13 F129

13 F130

16 F131

16 F132

13 F133

16 F134

16 F135

16 F136

16 F137

16 F138

16 F139

16 F140

F141

16 F142

16 F143

16 F144

13 F145

16 F146

43 F147

43 F148

43 F150

16 F153

16 F154

16 F155

16 F157

16 F158

13 F159

16 F160

16 F161

13 F162

16 F163

16 F164

13 F165

13 F166

15 F167

49 F168

50 F169

15 F170

15 F171

15 F172

15 F173

15 F174

13 F175

13 F176

13 F177

13 F178

13 F180

13 F181

13 F182

13 F183

13 F184

43 F185

13 F186

43 F187

43 F188

43 F189

43 F190

43 F191

43 F192

43 F193

13 F194

47 F195

47 F196

13 F197

13 F198

13 F199

47 F200

13 F201

13 F202

13 F203

13 F204

13 F205

13 F206

13 F207

48 F208

48 F209

48 F210

13 F211

13 F212

43 F213

47 F214

13 F215

44 F216

43 F217

13 *prepared according to example number

TABLE 3 Structure and Preparation Method for C Series Molecules No.Structure Prep.* C1

1 C2

1 C3

1 C4

1 C5

1 C6

1 C7

1 C8

1 C9

1 C10

1 C11

1 C12

1 C13

1 C14

1 C15

1 C16

1 C17

1 C18

1 C19

1 C20

1 C21

2 C22

3 C23

4 C24

5 C25

5, 7 C26

5 C27

5, 7 C28

6 C29

6 C30

6 C31

6 C32

7 C33

7 C34

8 C35

8 C36

8 C37

8 C38

8 C39

8 C40

8 C41

8 C42

9 C43

10 C44

10 C45

10 C46

11 C47

11 C48

11 C49

11 C50

11 C51

11 C52

12 C53

12 C54

12 C55

19 C56

19 C57

20 C58

20 C59

21 C60

21 C61

21 C62

21 C63

21 C64

21 C65

21 C66

21 C67

21 C68

22 C69

22 C70

22 C71

22 C72

22 C73

23 C74

24 C75

25 C76

26 C77

27 C78

28 C79

29 C80

30 C81

30 C82

31 C83

32 C84

33 C85

34 C86

1 C87

1 C88

1 C89

1 C90

1 C91

1 C92

1 C94

1 C95

1 C96

1 C97

1 C98

1 C99

1 C100

1 C101

1 C102

1 C103

1 C104

1 C105

1 C106

1 C107

1 C108

1 C109

1 C110

1 C111

1 C112

1 C113

1 C114

1 C115

3 C116

3 C117

3 C118

7 C119

8 C120

8 C121

8 C122

8 C123

8 C124

8 C125

8 C126

8 C127

8 C128

8 C129

8 C130

8 C131

8 C132

8 C133

8 C134

8 C135

8 C136

8 C137

8 C138

8 C139

8 C140

8 C141

10 C142

10 C143

10 C144

10 C145

10 C146

10 C147

11 C148

11 C149

11 C150

11 C151

11 C152

11 C153

11 C154

11 C155

11 C156

11 C157

11 C158

11 C159

11 C160

11 C161

11 C162

12 C163

13 C164

21 C165

21 C166

21 C167

21 C168

21 C169

21 C170

21 C171

21 C172

21 C173

22 C174

30 C175

31 C176

34 C177

35 C178

36 C179

37 C180

38 C181

39 C182

40 C183

41 C184

42 C185

45 C186

45 C187

45 C188

46 C189

47 C190

49 C191

53 C192

53 C193

54 C194

55 C195

56 C196

57 C197

57 C198

57 C199

8 C200

10 C201

58 *prepared according to example number

TABLE 4 Analytical Data for Molecules in Table 2 Mp ¹³C NMR; No. (° C.)Mass (m/z) ¹H NMR ¹⁹F NMR; IR F1 635 ([M + H]⁺) ¹H NMR (400 MHz, ¹⁹F NMRCDCl₃) δ 7.88 (d, J = 1.6 Hz, (376 MHz, 1H), CDCl₃) δ 7.79 (dd, J = 8.1,1.7 Hz, −59.40, 1H), 7.61 (d, J = 8.1 Hz, −69.32 (d, J = 2.2 Hz), 1H),7.44 (s, 2H), −72.57, 7.26 (d, J = 7.8 Hz, −109.75-−115.20 (m) 1H), 6.98(t, J = 5.2 Hz, 1H), 5.85 (dd, J = 32.5, 9.6 Hz, 1H), 4.61 (p, J = 8.9Hz, 1H), 4.25 (d, J = 5.1 Hz, 2H), 3.91 (qd, J = 9.0, 6.4 Hz, 2H) F2 649([M + H]⁺) ¹H NMR (400 MHz, ¹⁹F NMR CDCl₃) δ 7.84 (d, J = 1.7 Hz, (376MHz, 1H), CDCl₃) δ 7.74 (dd, J = 8.0, 1.7 Hz, −59.29, 1H), 7.53 (d, J =8.1 Hz, −69.34 (d, J = 2.1 Hz), 1H), 7.47 (t, J = 6.4 Hz, −72.64, 1H),7.44 (s, −112.09 2H), 6.93 (d, J = 7.8 Hz, 1H), 5.83 (dd, J = 32.5, 9.5Hz, 1H), 4.92 (p, J = 7.1 Hz, 1H), 4.61 (p, J = 8.9 Hz, 1H), 3.83 (qdd,J = 8.8, 6.2, 2.5 Hz, 2H), 1.51 (d, J = 6.9 Hz, 3H) F3 659 ([M − H]⁻) ¹HNMR (400 MHz, ¹⁹F NMR CDCl₃) δ 7.89 (d, J = 1.7 Hz, (376 MHz, 1H),CDCl₃) δ 7.81 (dd, J = 8.1, 1.7 Hz, −58.76 (d, J = 1.4 Hz), 1H), 7.55(d, J = 8.1 Hz, −69.29 (d, J = 2.3 Hz), 1H), 7.43 (s, 2H), −72.65 (t, J= 1.3 Hz), 6.91 (t, J = 6.4 Hz, −112.04 (d, J = 12.9 Hz) 1H), 6.42 (s,1H), 5.85 (dd, J = 32.5, 9.6 Hz, 1H), 4.61 (p, J = 8.8 Hz, 1H), 3.96(qd, J = 9.1, 6.4 Hz, 2H), 1.78-1.64 (m, 2H), 1.23-1.13 (m, 2H) F4 646¹H NMR (400 MHz, ¹⁹F NMR ([M − H]⁻) CDCl₃) δ 7.87 (d, J = 1.6 Hz, (376MHz, 1H), CDCl₃) δ 7.79 (dd, J = 8.2, 1.7 Hz, −58.66, 1H), 7.54 (d, J =8.1 Hz, −69.31 (d, J = 2.3 Hz), 1H), 7.44 (s, 2H), −112.04 6.75 (s, 1H),6.62 (t, J = 5.7 Hz, 1H), 5.86 (dd, J = 32.6, 9.6 Hz, 1H), 4.61 (p, J =8.9 Hz, 1H), 3.31 (td, J = 7.1, 5.7 Hz, 2H), 1.62-1.53 (m, 2H), 1.39 (q,J = 7.0 Hz, 2H), 1.15-1.01 (m, 2H), 0.77-0.57 (m, 1H), 0.50-0.36 (m,2H), 0.10-−0.01 (m, 2H) F5 619 ([M + H]⁺) ¹H NMR (400 MHz, ¹⁹F NMRCDCl₃) δ 7.87 (d, J = 1.6 Hz, (376 MHz, 1H), CDCl₃) δ 7.79 (dd, J = 8.1,1.7 Hz, −58.65, 1H), 7.54 (d, J = 8.1 Hz, −69.31 (d, J = 2.3 Hz) 1H),7.44 (s, 2H), −112.03 6.68 (s, 1H), 6.57 (t, J = 5.9 Hz, 1H), 5.95-5.71(m, 2H), 5.22 (dq, J = 17.1, 1.6 Hz, 1H), 5.14 (dq, J = 10.3, 1.4 Hz,1H), 4.61 (p, J = 8.8 Hz, 1H), 3.92-3.81 (m, 2H), 1.76-1.50 (m, 2H),1.18-0.99 (m, 2H) F6 579 ([M − H]⁻) ¹H NMR (400 MHz, ¹⁹F NMR CDCl₃) δ7.67 (t, J = 6.4 Hz, (376 MHz, 1H), CDCl₃) δ 7.48-7.34 (m, 5H), −69.45(d, J = 2.2 Hz), 7.11 (t, J = 5.2 Hz, 1H), −72.45, 5.73 (dd, J = 32.8,−111.78 9.6 Hz, 1H), 4.59 (p, J = 8.9 Hz, 1H), 4.24 (d, J = 5.2 Hz, 2H),3.90 (qd, J = 9.1, 6.4 Hz, 2H), 2.44 (s, 3H) F7 496 ¹H NMR (400 MHz, ¹⁹FNMR ([M − NHCH₂CF₃]⁺) CDCl₃) δ 7.47 (t, J = 6.5 Hz, (376 MHz, 1H), 7.43(s, CDCl₃) δ 2H), 7.40 (d, J = 1.3 Hz, −67.97-−70.44 (m), 1H), 7.38 (d,J = 1.1 Hz, −72.52, 2H), 6.69 (d, −110.05-−114.53 (m) J = 7.7 Hz, 1H),5.72 (dd, J = 32.8, 9.6 Hz, 1H), 4.99-4.70 (m, 1H), 4.58 (p, J = 8.9 Hz,1H), 3.89 (qd, J = 9.0, 6.4 Hz, 2H), 2.43 (s, 3H), 1.52 (d, J = 7.0 Hz,3H) F8 605 ([M − H]⁻) ¹H NMR (400 MHz, ¹⁹F NMR CDCl₃) δ 7.43 (s, (376MHz, 1H), 7.40 (d, J = 1.7 Hz, CDCl₃) δ 1H), 7.34 (d, J = 8.0 Hz, −69.43(d, J = 2.3 Hz), 1H), 7.18 (t, −72.54 J = 6.4 Hz, 1H), −111.77 6.57 (s,1H), 5.74 (dd, J = 32.8, 9.6 Hz, 1H), 4.58 (p, J = 8.9 Hz, 1H), 3.93(qd, J = 9.1, 6.4 Hz, 2H), 2.47 (s, 3H), 1.72-1.54 (m, 2H), 1.23-1.05(m, 2H) F9 566 ([M + H]⁺) ¹H NMR (400 MHz, ¹⁹F NMR CDCl₃) δ 7.43 (s,(376 MHz, 2H), 7.42 (s, 1H), CDCl₃) δ 7.41-7.36 (m, 1H), −69.42 (d, J =2.3 Hz), 7.36-7.32 (m, 1H), −111.73 7.19 (d, J = 8.1 Hz, 1H), 6.78-6.61(m, 1H), 5.92-5.65 (m, 2H), 5.22 (ddd, J = 17.2, 2.5, 1.4 Hz, 1H), 5.13(dt, J = 10.3, 1.6 Hz, 1H), 4.58 (p, J = 8.9 Hz, 1H), 3.87 (tdt, J =5.3, 3.4, 1.6 Hz, 2H), 2.46 (s, 3H), 1.67-1.56 (m, 2H), 1.09 (td, J =7.7, 4.9 Hz, 2H) F10 592 ([M − H]⁻) ¹H NMR (400 MHz, ¹⁹F NMR CDCl₃) δ7.43 (s, (376 MHz, 3H), 7.41-7.36 (m, CDCl₃) δ 2H), 6.73 (t, J = 5.7 Hz,−69.42 (d, J = 2.3 Hz), 1H), 6.57 (s, 1H), −110.57-−113.11 (m) 5.73 (dd,J = 32.8, 9.6 Hz, 1H), 4.58 (p, J = 8.9 Hz, 1H), 3.35 (td, J = 6.9, 5.7Hz, 2H), 2.48 (s, 3H), 1.67-1.56 (m, 2H), 1.41 (q, J = 6.9 Hz, 2H),1.17-1.04 (m, 2H), 0.67 (dddd, J = 14.9, 9.9, 5.2, 2.2 Hz, 1H),0.51-0.37 (m, 2H), 0.17-0.00 (m, 2H) F11 607 ([M + H]⁺) ¹H NMR (400 MHz,¹⁹F NMR CDCl₃) δ 7.82 (d, J = 1.6 Hz, (376 MHz, 1H), CDCl₃) δ 7.72 (dd,J = 8.0, 1.7 Hz, −59.16, 1H), 7.53 (d, J = 8.1 Hz, −69.32 (d, J = 2.3Hz), 1H), 7.44 (s, 2H), −110.35-−113.41 (m) 7.09 (dd, J = 7.7, 2.0 Hz,1H), 6.86 (t, J = 5.8 Hz, 1H), 5.92-5.61 (m, 2H), 5.24-5.03 (m, 2H),4.80 (p, J = 7.0 Hz, 1H), 4.61 (p, J = 8.9 Hz, 1H), 3.80 (tq, J = 5.7,1.8 Hz, 2H), 1.50 (d, J = 6.9 Hz, 3H) F12 633 ([M − H]⁻) ¹H NMR (400MHz, ¹⁹F NMR CDCl₃) δ (376 MHz, 7.90-7.79 (m, 1H), 7.74 (dd, J = 8.1,CDCl₃) δ 1.7 Hz, 1H), −59.16, 7.56 (d, J = 8.1 Hz, −69.33, 1H), 7.44 (s,2H), −108.63-−115.35 (m) 6.86 (dd, J = 7.8, 1.7 Hz, 1H), 6.52 (t, J =5.8 Hz, 1H), 5.97-5.68 (m, 1H), 4.71 (p, J = 7.0 Hz, 1H), 4.61 (p, J =8.9 Hz, 1H), 3.33 (dtdd, J = 20.2, 13.2, 7.0, 5.7 Hz, 2H), 1.49 (d, J =6.9 Hz, 3H), 1.39 (q, J = 7.0 Hz, 2H), 0.65 (dddt, J = 11.9, 8.4, 7.1,4.9 Hz, 1H), 0.47-0.34 (m, 2H), 0.11-0.01 (m, 2H) F13 661 ([M − H]⁻) ¹HNMR (400 MHz, ¹⁹F NMR CDCl₃) δ 7.86 (d, J = 1.8 Hz, (376 MHz, 1H),CDCl₃) δ 7.76 (dd, J = 8.1, 1.8 Hz, −59.12, 1H), 7.59 (d, J = 8.1 Hz,−69.32 (d, J = 2.3 Hz), 1H), 7.44 (s, 2H), −69.79, 6.90 (d, J = 7.5 Hz,−111.45-−112.65 (m) 1H), 5.82 (dd, J = 32.6, 9.6 Hz, 1H), 5.24-5.06 (m,1H), 4.61 (p, J = 8.9 Hz, 1H), 4.27 (dq, J = 14.9, 9.0 Hz, 1H), 3.85(dq, J = 14.9, 8.7 Hz, 1H), 3.26 (s, 3H), 1.48 (d, J = 6.8 Hz, 3H) F14553 ([M + H]⁺) ¹H NMR (500 MHz, ¹⁹F NMR CDCl₃) δ 7.43 (s, (471 MHz, 2H),7.42-7.33 (m, CDCl₃) δ 3H), 6.79 (d, J = 7.6 Hz, −69.42 (d, J = 8.9 Hz),1H), 6.72 (t, J = 5.9 Hz, −111.72 1H), 5.87-5.76 (m, 1H), 5.71 (dd, J =32.9, 9.6 Hz, 1H), 5.19 (dq, J = 17.1, 1.6 Hz, 1H), 5.12 (dq, J = 10.2,1.4 Hz, 1H), 4.76 (p, J = 7.0 Hz, 1H), 4.58 (p, J = 8.9 Hz, 1H), 3.88(tt, J = 5.7, 1.7 Hz, 2H), 2.44 (s, 3H), 1.51 (d, J = 7.0 Hz, 3H) F15581 ([M + H]⁺) ¹H NMR (500 MHz, ¹⁹F NMR CDCl₃) δ 7.43 (s, (471 MHz, 2H),7.42-7.34 (m, CDCl₃) δ 3H), 6.80 (d, J = 7.6 Hz, −69.43 (d, J = 8.7 Hz),1H), 6.61 (t, J = 5.8 Hz, −111.61 1H), 5.71 (dd, J = 32.9, 9.6 Hz, 1H),4.71 (p, J = 7.0 Hz, 1H), 4.58 (p, J = 8.9 Hz, 1H), 3.44-3.20 (m, 2H),2.45 (s, 3H), 1.50 (d, J = 6.9 Hz, 3H), 1.40 (q, J = 7.0 Hz, 2H), 0.66(dddd, J = 15.0, 10.1, 5.1, 2.3 Hz, 1H), 0.48-0.40 (m, 2H), 0.08-0.02(m, 2H) F16 623 ([M + H]⁺) ¹H NMR (500 MHz, ¹⁹F NMR CDCl₃) δ 7.84 (d, J= 1.6 Hz, (471 MHz, 1H), CDCl₃) δ 7.74 (dd, J = 8.1, 1.6 Hz, −59.19,1H), 7.55 (d, J = 8.1 Hz, −69.33 (d, J = 8.8 Hz), 1H), 7.44 (s, 2H),−111.97 (d, J = 19.7 Hz) 6.93 (dd, J = 7.8, 2.5 Hz, 1H), 6.54 (t, J =5.8 Hz, 1H), 5.93-5.71 (m, 1H), 4.73 (p, J = 7.0 Hz, 1H), 4.61 (p, J =8.9 Hz, 1H), 3.37-3.10 (m, 2H), 1.56-1.40 (m, 5H), 1.40-1.24 (m, 2H),0.88 (t, J = 7.3 Hz, 3H) F17 649 ([M + H]⁺) ¹H NMR (400 MHz, ¹⁹F NMRCDCl₃) δ 7.84 (d, J = 1.7 Hz, (471 MHz, 1H), CDCl₃) δ 7.74 (dd, J = 8.0,1.7 Hz, −59.36, 1H), 7.53 (d, J = 8.1 Hz, −69.81 (d, J = 5.9 Hz), 1H),7.47 (t, J = 6.4 Hz, −72.59 (d, J = 3.5 Hz), 1H), 7.44 (s, −90.26 2H),6.93 (d, J = 7.8 Hz, 1H), 5.92 (dd, J = 17.9, 11.1 Hz, 1H), 4.92 (p, J =7.1 Hz, 1H), 4.61 (p, J = 8.9 Hz, 1H), 3.83 (qdd, J = 8.8, 6.2, 2.5 Hz,2H), 1.51 (d, J = 6.9 Hz, 3H) F18 657 ([M − H]⁻) ¹H NMR (400 MHz, ¹⁹FNMR CDCl₃) δ 7.76 (d, J = 1.5 Hz, (376 MHz, 1H), CDCl₃) δ 7.59-7.46 (m,2H), −69.36 (d, J = 2.4 Hz), 7.43 (s, 3H), 7.00 (d, J = 7.6 Hz, −72.41,1H), −112.05 (d, J = 3.9 Hz) 5.77 (dd, J = 32.6, 9.6 Hz, 1H), 4.87 (p, J= 7.1 Hz, 1H), 4.58 (p, J = 8.9 Hz, 1H), 3.90 (qd, J = 9.0, 6.3 Hz, 2H),1.55 (d, J = 6.9 Hz, 3H) F19 645 ([M + H]⁺) ¹H NMR (400 MHz, ¹⁹F NMRCDCl₃) δ 7.78 (d, J = 1.2 Hz, (376 MHz, 1H), 7.55 (d, CDCl₃) δ J = 1.8Hz, 2H), −69.37, 7.43 (s, 2H), 7.37 (t, J = 6.4 Hz, −72.35, 1H), 7.20(t, −112.02 J = 5.2 Hz, 1H), 5.78 (dd, J = 32.6, 9.6 Hz, 1H), 4.59 (p, J= 8.9 Hz, 1H), 4.27 (d, J = 5.2 Hz, 2H), 3.94 (qd, J = 9.0, 6.4 Hz, 2H)F20 675 ([M − H]⁻) ¹H NMR (400 MHz, ¹⁹F NMR CDCl₃) δ 7.86 (d, J = 1.8Hz, (376 MHz, 1H), CDCl₃) δ 7.76 (dd, J = 8.1, 1.7 Hz, −59.16, 1H), 7.59(d, J = 8.2 Hz, −69.59, 1H), 7.44 (s, 2H), −111.89 (t, J = 9.4 Hz) 6.82(d, J = 7.7 Hz, 1H), 5.82 (dd, J = 32.6, 9.6 Hz, 1H), 5.22-5.07 (m, 1H),4.61 (p, J = 8.9 Hz, 1H), 4.37 (dq, J = 15.0, 9.1 Hz, 1H), 3.91-3.38 (m,3H), 1.49 (d, J = 6.8 Hz, 3H), 1.32 (t, J = 7.1 Hz, 3H) F21 668 ([M −H]⁻) ¹H NMR (400 MHz, ¹⁹F NMR CDCl₃) δ 7.76 (d, J = 1.7 Hz, (376 MHz,1H), CDCl₃) δ 7.56 (dd, J = 8.1, 1.7 Hz, −69.34 (d, J = 2.3 Hz), 1H),7.49 (d, J = 8.1 Hz, −72.34, 1H), 7.43 (s, 2H), −112.02 (d, J = 13.4 Hz)7.07 (t, J = 6.5 Hz, 1H), 6.81 (s, 1H), 5.79 (dd, J = 32.6, 9.6 Hz, 1H),4.59 (p, J = 8.9 Hz, 1H), 3.94 (qd, J = 9.1, 6.4 Hz, 2H), 1.74-1.62 (m,2H), 1.23-1.17 (m, 2H) F22 599 ([M − H]⁻) ¹H NMR (400 MHz, ¹⁹F NMRCDCl₃) δ 7.66 (d, J = 8.1 Hz, (376 MHz, 1H), 7.59 (d, CDCl₃) δ J = 1.7Hz, 1H), −69.37 (d, J = 2.4 Hz), 7.58-7.52 (m, 1H), −72.40, 7.52-7.46(m, 2H), −112.09 7.43 (s, 2H), 5.80 (dd, J = 32.6, 9.7 Hz, 1H), 4.59 (p,J = 8.9 Hz, 1H), 4.29 (d, J = 5.1 Hz, 2H), 3.92 (qd, J = 9.0, 6.4 Hz,2H) F23 613 ([M − H]⁻) ¹H NMR (400 MHz, ¹⁹F NMR CDCl₃) δ 7.63 (t, J =6.4 Hz, (376 MHz, 1H), 7.59 (d, CDCl₃) δ J = 8.1 Hz, 1H), −68.04-−70.81(m), 7.56 (d, J = 1.6 Hz, 1H), −72.46, 7.47 (dd, J = 8.2, 1.7 Hz,−112.10 1H), 7.43 (s, 2H), 7.31 (d, J = 7.6 Hz, 1H), 5.78 (dd, J = 32.6,9.6 Hz, 1H), 4.92 (p, J = 7.1 Hz, 1H), 4.58 (p, J = 8.9 Hz, 1H), 3.88(pt, J = 12.1, 6.1 Hz, 2H), 1.55 (d, J = 7.0 Hz, 3H) F24 677 ([M − H]⁻)¹H NMR (400 MHz, ¹⁹F NMR CDCl₃) δ 7.87 (d, J = 1.7 Hz, (376 MHz, 1H),CDCl₃) δ 7.77 (dd, J = 8.2, 1.7 Hz, −59.12, 1H), 7.62 (d, J = 8.1 Hz,−69.27, 1H), 7.44 (s, 2H), −69.31 (d, J = 2.3 Hz), 6.55 (d, J = 8.1 Hz,−111.89 (d, 1H), 5.82 (dd, J = 32.5, J = 3.4 Hz) 9.6 Hz, 1H), 5.18 (p, J= 7.2 Hz, 1H), 4.61 (p, J = 8.9 Hz, 1H), 4.45 (dq, J = 17.1, 8.7 Hz,1H), 4.07 (dd, J = 16.0, 8.0 Hz, 1H), 3.91 (s, 3H), 1.50 (d, J = 6.9 Hz,3H) F25 685 ([M − H]⁻) ¹H NMR (400 MHz, ¹⁹F NMR CDCl₃) δ 7.77 (d, J =1.6 Hz, (376 MHz, 1H), CDCl₃) δ 7.60-7.48 (m, 2H), −69.37 (d, J = 2.3Hz), 7.43 (s, 2H), 7.10 (d, J = 7.7 Hz, −69.56, 1H), −108.63-−118.42 (m)5.77 (dd, J = 32.6, 9.6 Hz, 1H), 5.27-5.08 (m, 1H), 4.59 (p, J = 8.9 Hz,1H), 4.37 (dq, J = 15.1, 9.1 Hz, 1H), 3.93-3.32 (m, 3H), 1.52 (d, J =6.8 Hz, 3H), 1.32 (t, J = 7.2 Hz, 3H) F26 591 ([M + H]⁺) ¹H NMR (400MHz, ¹⁹F NMR CDCl₃) δ (376 MHz, 7.47-7.36 (m, 5H), 6.95 (t, J = 6.5 Hz,CDCl₃) δ 1H), 6.30 (d, −72.51, J = 7.5 Hz, 1H), −95.16, 5.78 (dd, J =34.0, 9.8 Hz, −95.18, 1H), 4.72 (p, J = 7.0 Hz, −114.28 1H), 4.26 (td, J= 14.3, 9.8 Hz, 1H), 4.10-3.83 (m, 2H), 2.46 (s, 3H), 1.65 (t, J = 18.4Hz, 3H), 1.51 (d, J = 7.0 Hz, 3H) F27 705 ([M + H]⁺) ¹H NMR (400 MHz,¹⁹F NMR CDCl₃) δ 7.87 (d, J = 1.7 Hz, (376 MHz, 1H), CDCl₃) δ 7.77 (dd,J = 8.2, 1.8 Hz, −59.12, 1H), 7.62 (d, J = 8.1 Hz, −69.31, 1H), 7.44 (s,2H), −111.88 6.54 (d, J = 8.1 Hz, 1H), 6.03 (ddt, J = 16.8, 10.3, 6.4Hz, 1H), 5.82 (dd, J = 32.5, 9.6 Hz, 1H), 5.47 (m, 2H), 5.21 (q, J = 7.2Hz, 1H), 4.57 (m, 4H), 4.04 (dd, J = 15.8, 8.1 Hz, 1H), 1.49 (d, J = 6.9Hz, 3H) F28 625 ([M − H]⁻) ¹H NMR (400 MHz, ¹⁹F NMR CDCl₃) δ 7.67 (d, J= 8.1 Hz, (376 MHz, 1H), 7.62 (d, CDCl₃) δ J = 1.7 Hz, 1H), −69.34 (d, J= 2.3 Hz), 7.55 (dd, J = 8.2, 1.7 Hz, −72.48, 1H), 7.42 (s, 2H), −112.01(d, J = 14.3 Hz) 7.00 (t, J = 6.4 Hz, 1H), 6.80 (s, 1H), 5.80 (dd, J =32.5, 9.6 Hz, 1H), 4.59 (p, J = 8.9 Hz, 1H), 3.93 (dqd, J = 22.4, 9.1,6.6 Hz, 2H), 1.79-1.64 (m, 2H), 1.24-1.16 (m, 2H) F29 643 ([M − H]⁻) ¹HNMR (400 MHz, ¹⁹F NMR CDCl₃) δ (376 MHz, 7.89-7.82 (m, 1H), 7.75 (dd, J= 8.2, CDCl₃) δ 1.8 Hz, 1H), −59.16, 7.54 (d, J = 8.1 Hz, −72.59, 1H),7.42 (s, 2H), −93.24-−97.00 (m), 7.15 (t, J = 6.5 Hz, −114.71 1H), 6.62(d, J = 7.7 Hz, 1H), 5.90 (dd, J = 33.8, 9.8 Hz, 1H), 4.84 (p, J = 7.1Hz, 1H), 4.28 (td, J = 14.3, 9.7 Hz, 1H), 3.98-3.82 (m, 2H), 1.65 (t, J= 18.4 Hz, 3H), 1.51 (d, J = 6.9 Hz, 3H) F30 629 ([M − H]⁻) ¹H NMR (400MHz, ¹⁹F NMR CDCl₃) δ 7.83 (d, J = 1.7 Hz, (376 MHz, 1H), CDCl₃) δ 7.73(dd, J = 8.1, 1.7 Hz, −59.27, 1H), 7.53 (d, J = 8.1 Hz, −69.37 (d, J =2.2 Hz), 1H), 7.45 (d, J = 7.2 Hz, −109.45-−115.35 (m), 3H), 7.16 (d,−122.98 (d, J = 8.9 Hz) J = 7.8 Hz, 1H), 6.02-5.51 (m, 2H), 4.88 (p, J =7.0 Hz, 1H), 4.61 (p, J = 8.9 Hz, 1H), 3.71-3.37 (m, 2H), 1.49 (d, J =6.9 Hz, 3H) F31 639 ([M − H]⁻) ¹H NMR (400 MHz, ¹⁹F NMR CDCl₃) δ 7.76(d, J = 1.1 Hz, (376 MHz, 1H), 7.52 (d, CDCl₃) δ J = 1.1 Hz, 2H), −69.36(d, J = 2.2 Hz), 7.43 (s, 2H), 7.15 (t, J = 6.2 Hz, −111.99, 1H), 6.96(d, −122.83 J = 7.6 Hz, 1H), 6.05-5.60 (m, 2H), 4.82 (p, J = 7.1 Hz,1H), 4.58 (p, J = 8.9 Hz, 1H), 3.78-3.48 (m, 2H), 1.54 (d, J = 7.0 Hz,3H) F32 595 ([M − H]⁻) ¹H NMR (400 MHz, ¹⁹F NMR CDCl₃) δ 7.63 (d, J =8.1 Hz, (376 MHz, 1H), 7.57 (d, CDCl₃) δ J = 1.7 Hz, 1H), −69.37 (d, J =2.8 Hz), 7.48 (dd, J = 8.2, 1.8 Hz, −110.57-−115.35 (m), 1H), 7.43 (s,2H), −122.85 7.31 (t, J = 6.2 Hz, 1H), 7.24 (d, J = 7.5 Hz, 1H),6.05-5.64 (m, 2H), 4.86 (p, J = 7.0 Hz, 1H), 4.58 (p, J = 8.9 Hz, 1H),3.72-3.47 (m, 2H), 1.54 (d, J = 6.9 Hz, 3H) F33 110-113 701 ([M + H]⁺)¹H NMR (400 MHz, DMSO-d₆) δ 8.84 (d, J = 7.2 Hz, 1H), 8.64 (t, J = 6.4Hz, 1H), 8.11 (s, 1H), 8.06 (d, J = 7.6 Hz, 1H), 7.96 (s, 2H), 7.90-7.89(m, 1H), 7.67 (d, J = 7.6 Hz, 1H), 6.85 (dd, J = 36.0, 10.0 Hz, 1H),5.21-5.20 (m, 1H), 4.53-4.59 (m, 1H), 4.03-3.85 (m, 2H), 1.30 (d, J =6.8 Hz, 3H) F34 89-92 713 ([M + H]⁺) ¹H NMR (400 MHz, DMSO-d₆) δ 9.09(br s, 1H), 8.16-8.12 (m, 2H), 8.09 (d, J = 8.4 Hz, 1H), 8.01 (d, J =8.4 Hz, 1H), 7.96 (s, 2H), 7.91-7.90 (m, 1H) 6.85 (dd, J = 35.6, 10.0,Hz, 1H), 5.22-5.17 (m, 1H), 3.97-3.89 (m, 2H), 1.40-1.37 (m, 2H),1.03-1.01 (m, 2H) F35 124-127 686 ([M + H]⁺) ¹H NMR (400 MHz, DMSO-d₆) δ8.80 (t, J = 6.0 Hz, 1H), 8.62 (t, J = 6.4 Hz, 1H), 8.11 (s, 1H), 8.08(d, J = 8.0 Hz, 1H), 7.96 (s, 2H), 7.90 (s, 1H), 7.70 (d, J = 7.6 Hz,1H), 6.85 (dd, J = 36.0, 10.0 Hz, 1H), 5.21-5.20 (m, 1H), 3.96-3.87 (m,4H) F36 85-87 631 ([M + H]⁺) ¹H NMR (400 MHz, DMSO-d₆) δ 8.84 (d, J =7.2 Hz, 1H), 8.63 (t, J = 6.4 Hz, 1H), 8.10 (s, 1H), 8.05-8.03 (m, 2H),8.00 (d, J = 6.4 Hz, 1H), 7.67 (d, J = 8.0 Hz, 1H), 6.84 (dd, J = 36.0,10.0 Hz, 1H), 5.21-5.20 (m, 1H), 4.53-4.59 (m, 1H), 4.05-3.85 (m, 2H),1.30 (d, J = 7.2 Hz, 3H) F37 56-58 643 ([M + H]⁺) ¹H NMR (400 MHz,DMSO-d₆) δ 9.10 (br s, 1H), 8.16 (t, J = 6.4 Hz, 1H), 8.11 (s, 1H), 8.08(d, J = 8.4 Hz, 1H), 8.02 (s, 1H), 8.00 (d, J = 6.4 Hz, 2H), 6.84 (dd, J= 36.0, 10.4 Hz, 1H), 5.24-5.21 (m, 1H), 3.95-3.87 (m, 2H), 1.02 (t, J =4.4 Hz, 2H), 0.66 (t, J = 4.8 Hz, 2H) F38 82-85 615 ([M − H]⁻) ¹H NMR(400 MHz, DMSO-d₆) δ 8.88 (t, J = 6.0 Hz, 1H), 8.61 (t, J = 6.4 Hz, 1H),8.10 (s, 1H), 8.07 (d, J = 8.0 Hz, 1H), 8.00 (d, J = 6.4 Hz, 2H), 7.71(d, J = 8.4 Hz, 1H), 6.83 (dd, J = 35.6, 10.4 Hz, 1H), 5.24-5.23 (m,1H), 4.05-3.88 (m, 4H) F39 66-68 625 ([M + H]⁺) ¹H NMR (400 MHz,DMSO-d₆) δ 9.10 (s, 1H), 8.18-7.99 (m, 4H), 7.80 (s, 2H), 7.67 (s, 1H),6.88 (dd, J = 36.0, 10.2 Hz, 1H), 5.24-5.18 (m, 1H), 3.99-3.87 (m, 2H),1.09-0.98 (m, 2H), 0.97-0.87 (m, 2H) F40 101-103 590 ([M + H]⁺) ¹H NMR(300 MHz, DMSO-d₆) δ 8.80 (t, J = 5.7 Hz, 1H), 8.64 (t, J = 6.0 Hz, 1H),8.12 (s, 1H), 8.08 (d, J = 8.1 Hz, 1H), 7.81 (s, 2H), 7.71-7.69 (m, 2H),6.87 (dd, J = 36.0, 10.2 Hz, 1H), 5.24-5.18 (m, 1H), 4.02-3.90 (m, 4H)F41 599 ([M + H]⁺) ¹H NMR (400 MHz, IR (thin film) DMSO-d₆) δ 9.10 (s,3463, 3289, 1H), 8.17-8.07 (m, 1682, 1168, 3H), 8.02 (d, J = 8.4 Hz, 666cm⁻¹ 2H), 7.75 (d, J = 8.8 Hz, 1H), 7.67 (d, J = 8.8 Hz, 1H), 6.84 (dd,J = 36.0, 10.2 Hz, 1H), 5.21-5.16 (m, 1H), 3.97-3.89 (m, 2H), 1.40-1.37(m, 2H), 1.02-0.98 (m, 2H) F42 613 ([M + H]⁺) ¹H NMR (400 MHz, IR (thinfilm) DMSO-d₆) δ 8.84 (d, 3412, 2924, J = 8.0 Hz, 1H), 1652, 1275 cm⁻¹8.64 (t, J = 6.4 Hz, 1H), 8.10 (s, 1H), 8.05 (t, J = 6.4 Hz, 2H), 7.74(d, J = 8.8 Hz, 1H), 7.69-7.64 (m, 2H), 6.83 (dd, J = 35.6, 9.6 Hz, 1H),5.20-5.16 (m, 1H), 4.52-4.49 (m, 1H), 4.01-3.87 (m, 2H), 1.32-1.09 (m,3H) F43 599 ([M + H]⁺) ¹H NMR (400 MHz, IR (thin film) DMSO-d₆) δ 8.88(t, J = 6.0 Hz, 3348, 2924, 1H), 1657, 607 cm⁻¹ 8.63 (t, J = 6.4 Hz,1H), 8.11 (s, 1H), 8.07 (d, J = 8.0 Hz, 1H), 8.00 (d, J = 1.2 Hz, 1H),7.74-7.65 (m, 3H), 6.83 (dd, J = 36.0, 10.0 Hz, 1H), 5.21-5.16 (m, 1H),4.00-3.92 (m, 4H) F44 73-76 735 ([M + H]⁺) ¹H NMR (300 MHz, DMSO-d₆) δ8.85 (d, J = 7.5 Hz, 1H), 8.63 (s, 1H), 8.18-7.97 (m, 4H), 7.67 (d, J =8.1 Hz, 1H), 6.87 (dd, J = 36.3, 10.2 Hz, 1H), 5.25-5.19 (m, 1H),4.53-4.49 (m, 1H), 4.00-3.86 (m, 2H), 1.30 (d, J = 7.2 Hz, 3H) F45 81-84747 ([M + H]⁺) ¹H NMR (300 MHz, DMSO-d₆) δ 9.10 (s, 1H), 8.17-7.96 (m,6H), 6.87 (dd, J = 35.7, 10.2 Hz, 1H), 5.26-5.19 (m, 1H), 3.99-3.87 (m,2H), 1.41-1.38 (m, 2H), 1.03-0.99 (m, 2H) F46  99-102 721 ([M + H]⁺) ¹HNMR (300 MHz, DMSO-d₆) δ 8.87 (d, J = 5.7 Hz, 1H), 8.62 (d, J = 6.3 Hz,1H), 8.18-8.05 (m, 4H), 7.71 (d, J = 6.3 Hz, 1H), 6.87 (dd, J = 36.0,10.2 Hz, 1H), 5.26-5.19 (m, 1H), 4.02-3.90 (m, 4H) F47 613 ([M − H]⁻) ¹HNMR (400 MHz, ¹⁹F NMR CDCl₃) δ 7.77 (d, J = 8.1 Hz, (376 MHz, 1H), 7.61(d, CDCl₃) δ J = 1.6 Hz, 1H), −69.37 (d, J = 2.2 Hz), 7.51 (dd, J = 8.2,1.7 Hz, −69.89, 1H), 7.43 (s, 2H), −111.97 (d, J = 3.3 Hz) 7.41 (s, 1H),5.79 (dd, J = 32.6, 9.6 Hz, 1H), 4.59 (p, J = 8.9 Hz, 1H), 4.37 (d, J =4.1 Hz, 2H), 4.09 (q, J = 8.9 Hz, 2H), 3.19 (s, 3H) F48 657 ([M − H]⁻)¹H NMR (400 MHz, ¹⁹F NMR CDCl₃) δ 7.80 (d, J = 1.6 Hz, (376 MHz, 1H),7.63 (d, CDCl₃) δ J = 8.1 Hz, 1H), −69.36, 7.55 (dd, J = 8.2, 1.6 Hz,−69.88, 1H), 7.17 (q, J = 4.1 Hz, −111.89 1H), 5.77 (dd, J = 32.6, 9.6Hz, 1H), 4.59 (p, J = 8.9 Hz, 1H), 4.36 (d, J = 4.1 Hz, 2H), 4.19-4.02(m, 3H), 3.19 (s, 3H) F49 627 ([M − H]⁻) ¹H NMR (500 MHz, ¹⁹F NMR CDCl₃)δ 7.72 (d, J = 8.1 Hz, (471 MHz, 1H), 7.60 (d, CDCl₃) δ J = 1.7 Hz, 1H),−69.36 (d, J = 8.7 Hz), 7.50 (dd, J = 8.2, 1.7 Hz, −69.77 (t, J = 8.9Hz), 1H), 7.43 (s, 2H), −111.54-−112.50 (m) 7.30 (d, J = 7.3 Hz, 1H),5.77 (dd, J = 32.6, 9.5 Hz, 1H), 5.16 (p, J = 6.9 Hz, 1H), 4.58 (p, J =8.9 Hz, 1H), 4.39-4.23 (m, 1H), 3.84 (dq, J = 15.0, 8.9 Hz, 1H), 3.27(s, 3H), 1.51 (d, J = 6.8 Hz, 3H) F50 671 ([M − H]⁻) ¹H NMR (500 MHz,¹⁹F NMR CDCl₃) δ 7.78 (d, J = 1.7 Hz, (471 MHz, 1H), 7.58 (d, CDCl₃) δ J= 8.1 Hz, 1H), −69.36, 7.53 (dd, J = 8.1, 1.7 Hz, −69.75, 1H), 7.43 (s,2H), −111.15-−112.61 (m) 7.06 (d, J = 7.4 Hz, 1H), 5.75 (dd, J = 32.6,9.6 Hz, 1H), 5.22-5.09 (m, 1H), 4.58 (p, J = 8.8 Hz, 1H), 4.31 (dq, J =15.0, 9.1 Hz, 1H), 3.85 (dq, J = 15.0, 8.8 Hz, 1H), 3.27 (d, J = 0.8 Hz,3H), 1.51 (d, J = 6.8 Hz, 3H) F51 631 ([M − H]⁻) ¹H NMR (400 MHz, ¹⁹FNMR CDCl₃) δ 7.88 (d, J = 1.7 Hz, (471 MHz, 1H), CDCl₃) δ 7.81-7.72 (m,1H), −59.33, 7.64 (d, J = 8.0 Hz, 1H), −69.31, 7.44 (s, 2H), 6.88 (s,−69.90, 1H), 5.83 (dd, J = 32.5, −111.89 (d, J = 32.2 Hz) 9.6 Hz, 1H),4.61 (p, J = 8.9 Hz, 1H), 4.34 (d, J = 4.1 Hz, 2H), 4.16-4.00 (m, 2H),3.22-3.15 (m, 3H) F52 66-68 638 ([M − H]⁻) ¹H NMR (400 MHz, DMSO-d₆) δ7.86 (s, 1H), 7.80 (d, J = 8.4 Hz, 1H), 7.58 (d, J = 8.0 Hz, 1H), 7.42(s, 1H), 7.38-7.37 (m, 1H), 6.74-6.69 (m, 1H), 6.40 (d, J = 7.2 Hz, 1H),5.89-5.74 (m, 2H), 4.78-4.71 (m, 1H), 4.64-4.55 (m, 1H), 3.97-3.89 (m,2H), 1.52 (d, J = 7.2 Hz, 3H) F53 607 ([M + H]⁺) ¹H NMR (300 MHz, IR(thin film) DMSO-d₆) δ 9.23 (d, 3440, 2927, J = 8.1 Hz, 1H), 1716, 1175cm⁻¹ 8.13 (s, 1H), 8.04 (s, 3H), 7.66 (d, J = 8.1 Hz, 1H), 6.88 (dd, J =35.6, 10.2 Hz, 1H), 5.28-5.21 (m, 1H), 5.02-4.93 (m, 1H), 4.64-4.59 (m,1H), 4.09-4.00 (m, 1H), 3.57-3.31 (m, 2H), 1.23-1.19 (br s, 3H) F54 661([M − H]⁻) ¹H NMR (400 MHz, ¹⁹F NMR CDCl₃) δ 7.87 (d, J = 1.7 Hz, (471MHz, 1H), CDCl₃) δ 7.79 (dd, J = 8.1, 1.8 Hz, −58.82, 1H), 7.59 (d, J =8.1 Hz, −69.31, 1H), 7.44 (s, 2H), −73.25, 7.12 (t, J = 6.4 Hz, −111.881H), 5.83 (dd, J = 32.6, 9.6 Hz, 1H), 5.26 (s, 1H), 4.61 (p, J = 8.9 Hz,1H), 3.92 (dqd, J = 37.0, 9.1, 6.4 Hz, 2H), 1.70 (s, 6H) F55 762 ([M −H]⁻) ¹H NMR (400 MHz, ¹⁹F NMR CDCl₃) δ 7.86 (d, J = 1.7 Hz, (376 MHz,1H), CDCl₃) δ 7.77 (dd, J = 8.0, 1.7 Hz, −59.19 (d, J = 6.3 Hz), 1H),7.59 (d, J = 7.8 Hz, −69.31 (d, J = 2.3 Hz), 1H), 7.44 (s, 2H), −69.69(d, J = 12.5 Hz), 7.18 (s, 1H), 6.60 (d, −111.89; J = 73.8 Hz, 2H),rotamers 5.82 (dd, J = 32.5, 9.6 Hz, 1H), 4.88 (s, 1H), 4.59 (m, 1H),3.68 (d, J = 45.3 Hz, 1H), 1.52 (s, 12H); rotamers F56 658 ([M − H]⁻) ¹HNMR (400 MHz, ¹⁹F NMR CDCl₃) δ 7.86 (d, J = 1.7 Hz, (471 MHz, 1H),CDCl₃) δ 7.80 (dd, J = 8.1, 1.7 Hz, −58.79, 1H), 7.60 (d, J = 8.1 Hz,−66.61, 1H), 7.44 (s, 2H), −69.31, 6.57 (s, 1H), −111.93 5.85 (dd, J =32.5, 9.6 Hz, 1H), 4.61 (p, J = 8.9 Hz, 1H), 2.95 (dd, J = 8.6, 6.8 Hz,2H), 2.57-2.31 (m, 2H), 1.76-1.65 (m, 2H), 1.33-1.28 (m, 2H) F57 664([M + H]⁺) ¹H NMR (400 MHz, ¹⁹F NMR CDCl₃) δ 7.86 (d, J = 1.7 Hz, (376MHz, 1H), 7.76 (m, CDCl₃) δ 1H), 7.60 (d, J = 8.1 Hz, −59.12, 1H), 7.44(s, 2H), −69.31 (d, J = 2.3 Hz), 6.67 (d, J = 7.9 Hz, −69.40, 1H), 5.81(dd, J = 32.6, −111.85 9.6 Hz, 1H), 5.65 (m, 1H), 4.59 (m, 1H), 4.45(dq, J = 15.2, 8.9 Hz, 1H), 4.11 (s, 2H), 4.00 (dq, J = 15.2, 8.6 Hz,1H), 1.50 (d, J = 6.9 Hz, 3H) F58 657 ([M + H]⁺) ¹H NMR (400 MHz, ¹³CNMR CDCl₃) δ 7.87 (s, (101 MHz, 1H), 7.79 (d, J = 8.1 Hz, CDCl₃) δ 1H),169.85, 7.57-7.50 (m, 1H), 7.42 (s, 166.53, 2H), 6.91 (s, 1H), 157.06(d, 6.33 (s, 1H), J_(CF) = 252.8 Hz), 5.92 (dd, J = 33.7, 9.8 Hz, 136.98(d, J_(CF) = 5.7 Hz), 1H), 4.27 (td, J = 14.7, 135.96, 14.3, 9.7 Hz,132.74, 1H), 3.94 (ddd, J = 18.9, 131.21, 9.3, 6.5 Hz, 129.10, 2H), 1.64(t, J = 18.4 Hz, 128.60, 3H), 127.91, 1.28-1.16 (m, 3H), 127.33,0.93-0.84 (m, 1H) 127.29, 125.17, 124.32, 122.57-121.90 (m), 121.60,99.98, 53.13, 48.63-47.10 (m), 28.27, 23.04-22.23 (m), 19.91 F59 689 ([M− H]⁻) ¹H NMR (400 MHz, IR (thin film) DMSO-d₆) δ 8.85 (d, 3293, 2924, J= 8.0 Hz, 1H), 1651, 1170 cm⁻¹ 8.63 (t, J = 6.4 Hz, 1H), 8.10-8.00 (m,4H), 7.67 (d, J = 8.0 Hz, 1H), 6.84 (dd, J = 35.6, 10.4 Hz, 1H),5.25-5.20 (m, 1H), 4.53-4.49 (m, 1H), 4.02-3.87 (m, 2H), 1.30 (d, J =7.6 Hz, 3H) F60 703 ([M + H]⁺) ¹H NMR (400 MHz, IR (thin film) DMSO-d₆)δ 9.10 (s, 3437, 1663, 1H), 8.17-7.99 (m, 1119, 749 cm⁻¹ 6H), 6.85 (dd,J = 35.6, 10.0 Hz, 1H), 5.23-5.21 (m, 1H), 4.00-3.83 (m, 2H), 1.40-1.33(m, 2H), 1.03-1.00 (m, 2H) F61 105-107 626 ([M + H]⁺) ¹H NMR (400 MHz,CDCl₃) δ 7.88 (s, 1H) 7.79 (d, J = 8.4 Hz, 1H), 7.66 (d, J = 7.6 Hz,1H), 7.42 (s, 1H), 7.37 (s, 1H), 6.69-6.64 (m, 2H), 5.90-5.74 (m, 2H),4.62-4.57 (m, 1H), 4.22 (d, J = 5.6 Hz, 2H), 3.99-3.91 (m, 2H) F62 631([M + H]⁺) ¹H NMR (400 MHz, ¹³C NMR CDCl₃) δ 7.84 (s, (101 MHz, 1H),7.74 (dd, J = 8.1, CDCl₃) δ 1.7 Hz, 1H), 168.92, 7.56 (d, J = 8.1 Hz,167.79, 1H), 7.52 (t, J = 6.5 Hz, 157.06 (d, 1H), 7.42 (s, 2H), J_(CF) =253.1 Hz), 7.17 (t, J = 5.1 Hz, 136.92 (d, J_(CF) = 3.4 Hz), 1H), 5.91(dd, J = 33.8, 135.13, 9.7 Hz, 1H), 134.54, 4.38-4.20 (m, 3H), 133.45,3.87 (qd, J = 9.0, 6.4 Hz, 133.16, 2H), 1.65 (t, J = 18.4 Hz, 131.25,3H) 129.12, 127.70 (d, J_(CF) = 5.8 Hz), 125.22, 124.40, 122.83-122.35(m), 121.67, 103.78, 48.56-47.56 (m), 43.74, 40.64 (dd, J = 70.8, 35.6Hz), 23.38-21.79 (m) F63 593 ([M − H]⁻) ¹H NMR (400 MHz, ¹⁹F NMR CDCl₃)δ (471 MHz, 7.90-7.79 (m, 1H), 7.74 (dd, J = 8.1, CDCl₃) δ 1.7 Hz, 1H),−59.09, 7.56 (d, J = 8.1 Hz, −69.32, 1H), 7.44 (s, 2H), −111.85 6.88(dd, J = 7.8, 2.0 Hz, 1H), 6.50 (t, J = 5.6 Hz, 1H), 5.82 (ddd, J =32.6, 9.6, 0.8 Hz, 1H), 4.71 (p, J = 7.0 Hz, 1H), 4.59 (q, J = 8.9 Hz,1H), 3.27 (qd, J = 7.3, 5.6 Hz, 2H), 1.49 (d, J = 6.9 Hz, 3H), 1.12 (t,J = 7.3 Hz, 3H) F64 559 ([M − H]⁻) ¹H NMR (400 MHz, ¹⁹F NMR CDCl₃) δ7.65 (d, J = 8.1 Hz, (471 MHz, 1H), 7.58 (d, CDCl₃) δ J = 1.6 Hz, 1H),−69.37, 7.49 (dd, J = 8.2, 1.7 Hz, −111.86 1H), 7.43 (s, 2H), 7.10 (d, J= 7.5 Hz, 1H), 6.37 (t, J = 5.7 Hz, 1H), 5.77 (dd, J = 32.5, 9.6 Hz,1H), 4.70 (p, J = 7.0 Hz, 1H), 4.58 (p, J = 8.9 Hz, 1H), 3.40-3.15 (m,2H), 1.52 (d, J = 6.9 Hz, 3H), 1.16 (t, J = 7.3 Hz, 3H) F65 647 ([M −H]⁻) ¹H NMR (300 MHz, ¹⁹F NMR CDCl₃) δ 7.85 (d, J = 1.6 Hz, (471 MHz,1H), CDCl₃) δ 7.76 (dd, J = 8.1, 1.7 Hz, −59.09 (d, J = 16.2 Hz), 1H),7.57 (d, J = 8.1 Hz, −69.34, 1H), 7.49 (s, 2H), −74.46-−80.70 (m),7.41-7.17 (m, 2H), −111.92 (dd, 5.85 (dd, J = 32.6, J = 49.8, 9.6 Hz,1H), 32.3 Hz) 4.78-4.43 (m, 2H), 4.21 (d, J = 5.1 Hz, 2H), 1.32-1.27 (m,3H) F66 613 ([M − H]⁻) ¹H NMR (300 MHz, ¹⁹F NMR CDCl₃) δ (471 MHz,7.75-7.65 (m, 1H), 7.61 (d, J = 1.7 Hz, CDCl₃) δ 1H), −69.34, 7.52 (dd,J = 8.2, 1.8 Hz, −77.5, 1H), 7.43 (s, 2H), −111.95 7.34 (t, J = 5.0 Hz,1H), 7.12 (d, J = 9.4 Hz, 1H), 5.80 (dd, J = 32.6, 9.6 Hz, 1H),4.83-4.41 (m, 2H), 4.27 (dd, J = 5.1, 1.4 Hz, 2H), 1.34 (d, J = 7.0 Hz,3H) F67 703 ([M − H]⁻) ¹H NMR (400 MHz, ¹⁹F NMR CDCl₃) δ 7.98 (d, J =1.6 Hz, (471 MHz, 1H), CDCl₃) δ 7.65-7.59 (m, 1H), −69.34 (d, J = 8.9Hz), 7.52 (dd, J = 8.1, 1.7 Hz, −72.42, 1H), 7.43 (d, J = 4.6 Hz,−108.78-−113.05 (m) 2H), 7.35 (d, J = 8.1 Hz, 1H), 7.02 (d, J = 7.7 Hz,1H), 5.74 (dd, J = 32.6, 9.6 Hz, 1H), 4.90 (h, J = 7.0 Hz, 1H),4.70-4.45 (m, 1H), 3.88 (tddd, J = 14.9, 12.5, 8.9, 6.1 Hz, 2H), 1.56(d, J = 7.0 Hz, 3H) F68 649 ([M + H]⁺) ¹H NMR (500 MHz, ¹⁹F NMR CDCl₃) δ7.91 (d, J = 1.6 Hz, (471 MHz, 1H), CDCl₃) δ 7.90-7.81 (m, 1H), −60.56,7.49-7.42 (m, 1H), −69.37 (d, J = 8.9 Hz), 7.45 (s, 2H), 7.15 (t, J =6.5 Hz, −72.61 (t, J = 9.0 Hz), 1H), −112.15 (d, J = 32.7 Hz) 5.94-5.78(m, 1H), 4.63 (p, J = 8.7 Hz, 1H), 4.24 (s, 2H), 3.90 (m, 2H), 2.91 (s,3H) F69 607 ([M + H]⁺) ¹H NMR (300 MHz, IR (thin film) DMSO-d₆) δ 8.45(d, 3285, 2929, J = 7.2 Hz, 1H), 1653, 1167 cm⁻¹ 8.65 (t, J = 6.0 Hz,1H), 8.07-8.02 (m, 2H), 7.66 (d, J = 8.1 Hz, 1H), 7.45 (s, 2H), 6.78(dd, J = 36.0, 10.2 Hz, 1H), 4.95-4.89 (m, 1H), 4.53-4.48 (m, 1H),4.02-3.86 (m, 2H), 2.35 (s, 6H), 1.32 (d, J = 7.2 Hz, 3H) F70 619 ([M +H]⁺) ¹H NMR (300 MHz, IR (thin film) DMSO-d₆) δ 9.10 (s, 3339, 2925,1H), 8.17 (t, J = 6.6 Hz, 1661, 1165 cm⁻¹ 1H), 8.08 (s, 2H), 8.01 (d, J= 8.4 Hz, 1H), 7.44 (s, 2H), 6.79 (dd, J = 30.0, 9.9 Hz, 1H), 4.96-4.89(m, 1H), 3.96-3.90 (m, 2H), 2.35 (s, 6H), 1.40-1.29 (m, 2H), 1.08-1.01(m, 2H) F71 593 ([M + H]⁺) ¹H NMR (300 MHz, IR (thin film) DMSO-d₆) δ8.88 (t, J = 6.0 Hz 3321, 2918, 1H), 1654, 1166 cm⁻¹ 8.63 (t, J = 6.0Hz, 1H), 8.07 (s, 1H), 8.04 (s, 1H), 7.70 (d, J = 7.8 Hz, 1H), 7.45 (s,2H), 6.78 (dd, J = 35.7, 9.9 Hz, 1H), 4.96-4.89 (m, 1H), 4.02-3.90 (m,4H), 2.35 (s, 6H) F72 627 ([M + H]⁺) ¹H NMR (300 MHz, IR (thin film)DMSO-d₆) δ 8.97 (d, 3418, 2927, J = 7.8 Hz, 1H), 1652, 749 cm⁻¹ 8.11 (s,1H), 8.05 (d, J = 8.1 Hz, 1H), 7.81 (s, 2H), 7.68 (s, 1H), 7.60 (d, J =8.1 Hz, 1H), 6.87 (dd, J = 36.0, 10.2 Hz, 1H), 5.24-5.17 (m, 1H),4.99-4.97 (m, 1H), 4.29-4.14 (m, 2 H), 3.23 (s, 3H), 1.29 (d, J = 6.8Hz, 3H) F73 625 ([M − H]⁻) ¹H NMR (400 MHz, IR (thin film) DMSO-d₆) δ8.97 (d, 3435, 2924, J = 7.6 Hz, 1H), 1651, 750 cm⁻¹ 8.11 (s, 1H), 8.04(d, J = 8.0 Hz, 1H), 8.00 (s, 2H), 7.74 (d, J = 8.4 Hz, 1H), 7.67 (d, J= 6.8 Hz, 1H), 7.59 (d, J = 8.4 Hz, 1H), 6.83 (dd, J = 35.6, 9.8 Hz,1H), 5.20-5.16 (m, 1H), 4.98-4.94 (m, 1H), 4.24-4.11 (m, 2H), 3.22 (s,3H), 1.28 (d, J = 6.8 Hz, 3H) F74 613 ([M + H]⁺) ¹H NMR (400 MHz, IR(thin film) DMSO-d₆) δ 8.80 (t, J = 6.0 Hz, 3406, 2926, 1H), 1661, 749cm⁻¹ 8.12 (s, 1H), 8.07 (d, J = 8.8 Hz, 1H), 8.00 (s, 1H), 7.74-7.65 (m,3H), 6.83 (dd, J = 35.6, 10.0 Hz, 1H), 5.21-5.16 (m, 1H), 4.22-4.15 (m,4H), 3.14 (s, 3H) F75 693 ([M + H]⁺) ¹H NMR (300 MHz, IR (thin film)DMSO-d₆) δ 8.97 (d, 3412, 1652 cm⁻¹ J = 7.2 Hz, 1H), 8.10 (s, 1H),8.05-8.00 (m, 3H), 7.95 (s, 1H), 7.60 (d, J = 8.1 Hz, 1H), 6.86 (dd, J =35.7, 9.9 Hz, 1H), 5.26-5.19 (m, 1H), 4.99-4.94 (m, 1H), 4.34-4.08 (m,2H), 3.22 (s, 3H) F76 705 ([M + H]⁺) ¹H NMR (300 MHz, IR (thin film)DMSO-d₆) δ 8.81 (t, J = 5.4 Hz, 3411, 1661 cm⁻¹ 1H), 8.11 (s, 1H), 8.08(d, J = 8.4 Hz, 1H), 8.00 (s, 2H), 7.70 (d, J = 8.1 Hz, 1H), 6.86 (dd, J= 35.4, 9.9 Hz, 1H), 5.26-5.20 (m, 1H), 4.23-4.18 (m, 3H), 3.14 (s, 3H),1.26 (d, J = 7.2 Hz, 3H) F77 735 ([M + H]⁺) ¹H NMR (300 MHz, IR (thinfilm) DMSO-d₆) δ 8.79 (d, 3411, 1661 cm⁻¹ J = 5.4 Hz, 1H), 8.18-8.05 (m,4H), 7.70 (d, J = 8.1 Hz, 1H), 6.87 (dd, J = 36.3, 10.2 Hz, 1H)5.23-5.19 (m, 1H), 4.23-4.19 (m, 4H), 3.14 (s, 3H) F78 749 ([M + H]⁺) ¹HNMR (300 MHz, IR (thin film) DMSO-d₆) δ 8.97 (d, 3411, 1652 cm⁻¹ J = 6.6Hz, 1H), 8.17-8.02 (m, 4H), 7.60 (d, J = 8.1 Hz, 1H), 6.86 (dd, J =36.0, 9.6 Hz, 1H), 5.25-5.19 (m, 1H), 4.98-4.95 (m, 1H), 4.35-4.10 (m,2H), 3.22 (s, 3H), 1.28 (d, J = 6.0 Hz, 3H) F79 699 ([M − H]⁻) ¹H NMR(400 MHz, IR (thin film) DMSO-d₆) δ 8.81 (d, 3429, 2927, J = 8.0 Hz,1H), 1649, 1116 cm⁻¹ 8.61 (t, J = 6.0 Hz, 1H), 8.09 (s, 2H), 8.05 (d, J= 8.0 Hz, 1H), 7.85 (d, J = 8.0 Hz, 1H), 7.66 (d, J = 8.0 Hz, 1H), 7.61(d, J = 6.8 Hz, 1H), 6.81 (dd, J = 36.0, 9.6 Hz, 1H), 5.17-5.16 (m, 1H),4.53-4.49 (m, 1H), 4.01-3.86 (m, 2H), 1.30 (d, J = 6.8 Hz, 3H) F80 712([M − H]⁻) ¹H NMR (400 MHz, IR (thin film) DMSO-d₆) δ 9.08 (br 3436,2926, s, 1H), 1667, 1275, 8.13-8.08 (m, 2H), 8.06 (s, 750 cm⁻¹ 2H), 8.00(d, J = 8.0 Hz, 1H), 7.85 (d, J = 8.4 Hz, 1H), 7.61 (d, J = 8.4 Hz, 1H),6.85 (dd, J = 35.6, 10.0 Hz, 1H), 5.17-5.16 (m, 1H), 4.03-3.89 (m, 2H),1.42-1.33 (m, 2H), 1.03-1.01 (m, 2H) F81 643 ([M − H]⁻) ¹H NMR (400 MHz,IR (thin film) DMSO-d₆) δ 8.94 (d, 3432, 2927, J = 7.6 Hz, 1H), 1647,1262, 8.10 (s, 1H), 8.04 (d, J = 8.4 Hz, 749 cm⁻¹ 1H), 8.00 (d, J = 6.4Hz, 2H), 7.60 (d, J = 8.0 Hz, 1H), 6.82 (dd, J = 35.6, 10.4 Hz, 1H),5.23-5.21 (m, 1H), 4.99-4.93 (m, 1H), 4.32-4.26 (m, 1H), 4.15-4.02 (m,1H), 3.22 (s, 3H), 1.29 (d, J = 6.8 Hz, 3H) F82 629 ([M + H]⁺) ¹H NMR(400 MHz, IR (thin film) DMSO-d₆) δ 8.76 (t, J = 6.0 Hz, 3418, 2927,1H), 1651, 749 cm⁻¹ 8.10 (s, 1H), 8.07 (d, J = 8.4 Hz, 1H), 8.00 (d, J =6.0 Hz, 2H), 7.70 (d, J = 8.4 Hz, 1H), 6.82 (dd, J = 35.6, 9.6 Hz, 1H),5.23-5.22 (m, 1H), 4.39-4.36 (m, 1H), 4.23-4.19 (m, 3H), 3.14 (s, 3H)F83 715 ([M + H]⁺) ¹H NMR (300 MHz, IR (thin film) DMSO-d₆) δ 8.97 (d,3405, 2929, J = 8.1 Hz, 1H), 1651, 748 cm⁻¹ 8.11 (s, 1H), 8.05 (d, J =8.7 Hz, 1H), 7.96 (s, 2H), 7.90-7.89 (m, 1H), 7.60 (d, J = 8.4 Hz, 1H),6.87 (dd, J = 36.0, 10.2 Hz, 1H), 5.22-5.21 (m, 1H), 4.99-4.94 (m, 1H),4.34-4.08 (m, 2H), 3.22 (s, 3H), 1.29 (d, J = 6.9 Hz, 3H) F84 701 ([M +H]⁺) ¹H NMR (300 MHz, IR (thin film) DMSO-d₆) δ 8.80 (t, J = 5.4 Hz,3402, 2926, 1H), 1660, 748 cm⁻¹ 8.12 (s, 1H), 8.08-8.06 (m, 1H), 7.96(s, 2H), 7.90 (s, 1H), 7.70 (d, J = 8.1 Hz, 1H), 6.87 (dd, J = 36.0,10.2 Hz, 1H), 5.22-5.20 (m, 1H), 4.23-4.16 (m, 4H), 3.14 (s, 3H) F85 639([M + H]⁺) ¹H NMR (300 MHz, IR (thin film) CDCl₃) δ 7.88 (s, 3437, 2924,1H), 7.79 (d, J = 7.8 Hz, 1661, 1266, 1H), 7.64 (d, J = 7.8 Hz, 1170,764 cm⁻¹ 1H), 7.44 (s, 1H), 7.37 (s, 1H), 6.76-6.72 (m, 1H), 5.84-5.65(m, 2H), 5.47-5.31 (m, 1H), 4.64-4.60 (m, 1H), 4.34-4.31 (m, 2H),4.12-4.03 (q, J = 8.7 Hz, 2H), 3.17 (s, 3H) F86 85-88 653 ([M + H]⁺) ¹HNMR (300 MHz, CDCl₃) δ 7.86 (s, 1H), 7.79 (d, J = 8.1 Hz, 1H), 7.59 (d,J = 8.4 Hz, 1H), 7.43 (s, 1H), 7.37 (s, 1H), 7.01-6.90 (m, 1H),5.94-5.65 (m, 3H), 5.46-5.34 (m, 1H), 5.16-5.11 (m, 1H), 4.33-4.25 (m,1H), 3.88-3.80 (m, 1H), 3.26 (s, 3H), 1.54 (d, J = 6.9 Hz, 3H) F87 646([M + H]⁺) ¹H NMR (400 MHz, ¹⁹F NMR CDCl₃) δ 7.83 (d, J = 1.8 Hz, (471MHz, 1H), 7.73 (dt, CDCl₃) δ J = 9.0, 2.7 Hz, 1H), −59.32, 7.59-7.52 (m,2H), −72.56, 7.42 (d, J = 5.2 Hz, −102.60-−107.05 (m), 2H), 7.22-7.13(m, −115.08 1H), 5.91 (ddd, J = 33.9, 9.7, 1.6 Hz, 1H), 4.39-4.19 (m,2H), 3.85 (qd, J = 8.9, 6.3 Hz, 2H), 1.98-1.78 (m, 3H), 1.07 (t, J = 7.4Hz, 3H) F88 672 ([M + H]⁺) ¹H NMR (400 MHz, ¹⁹F NMR CDCl₃) δ 7.82 (d, J= 1.8 Hz, (471 MHz, 1H), CDCl₃) δ 7.73 (ddd, J = 8.3, 4.2, −58.73, 1.6Hz, 1H), −72.6, 7.46 (dd, J = 8.1, 4.5 Hz, −101.74-−107.92 (m), 1H),7.42 (s, 2H), −115.12 6.92 (q, J = 6.1 Hz, 2H), 5.92 (dd, J = 33.9 9.7Hz, 1H), 4.31 (td, J = 14.6, 9.8 Hz, 1H), 3.89 (qd, J = 9.0, 6.4 Hz,2H), 2.02 1.72 (m, 2H), 1.64 1.56 (m, 2H), 1.18 1.12 (m, 2H), 1.07 (t, J= 7.4 Hz, 3H) F89 687 ([M − H]⁻) ¹H NMR (400 MHz, ¹⁹F NMR CDCl₃) δ (471MHz, 7.98-7.84 (m, 1H), 7.80 (dd, J = 8.1, CDCl₃) δ 1.7 Hz, 1H), −58.56,7.53 (d, J = 8.1 Hz, −66.16, 1H), 7.44 (s, 2H), −69.29, 6.61 (d, J = 3.8Hz, −111.68 2H), 5.86 (dd, J = 32.5, 9.6 Hz, 1H), 4.61 (p, J = 8.9 Hz,1H), 3.34 (q, J = 6.6 Hz, 2H), 2.27-2.07 (m, 2H), 1.88-1.72 (m, 2H),1.72-1.54 (m, 2H), 1.17-1.04 (m, 2H) F90 673 ([M − H]⁻) ¹H NMR (400 MHz,¹⁹F NMR CDCl₃) δ 7.87 (d, J = 1.6 Hz, (471 MHz, 1H), CDCl₃) δ 7.80 (dd,J = 8.0, 1.7 Hz, −58.66, 1H), 7.54 (d, J = 8.1 Hz, −65.10 (d, J = 10.7Hz), 1H), 7.44 (s, 2H), −69.30, 6.79 (t, J = 6.1 Hz, −111.97 1H), 6.59(s, 1H), 5.86 (dd, J = 32.5, 9.6 Hz, 1H), 4.61 (p, J = 8.8 Hz, 1H), 3.53(q, J = 6.3 Hz, 2H), 2.34 (qt, J = 10.8, 6.5 Hz, 2H), 1.70-1.57 (m, 2H),1.22-1.07 (m, 2H) F91 647 ([M − H]⁻) ¹H NMR (400 MHz, ¹⁹F NMR CDCl₃) δ(471 MHz, 7.94-7.83 (m, 1H), 7.79 (dd, J = 8.1, CDCl₃) δ 1.7 Hz, 1H),−58.57, 7.53 (d, J = 8.1 Hz, −69.30, 1H), 7.44 (s, 2H), −111.96 (d, J =32.3 Hz) 6.65 (s, 1H), 6.47 (t, J = 5.5 Hz, 1H), 5.85 (dd, J = 32.6, 9.6Hz, 1H), 4.61 (p, J = 8.9 Hz, 1H), 3.26 (ddd, J = 8.6, 7.4, 5.7 Hz, 2H),1.66 (d, J = 3.0 Hz, 1H), 1.63-1.57 (m, 2H), 1.39 (q, J = 7.1 Hz, 2H),1.18-1.00 (m, 2H), 0.91 (d, J = 6.6 Hz, 6H) F92 655 ([M − H]⁻) ¹H NMR(400 MHz, ¹⁹F NMR CDCl₃) δ 7.87 (d, J = 1.7 Hz, (471 MHz, 1H), CDCl₃) δ7.80 (dd, J = 8.2, 1.8 Hz, −58.70, 1H), 7.55 (d, J = 8.0 Hz, −69.31,1H), 7.44 (s, 2H), −96.76, 6.76 (t, J = 6.2 Hz, −111.99 (d, J = 32.5 Hz)1H), 6.54 (s, 1H), 5.85 (dd, J = 32.5, 9.6 Hz, 1H), 4.61 (p, J = 8.9 Hz,1H), 3.68 (td, J = 13.6, 6.3 Hz, 2H), 1.71-1.65 (m, 2H), 1.60 (t, J =18.6 Hz, 3H), 1.23-1.10 (m, 2H) F93 645 ([M − H]⁻) ¹H NMR (400 MHz, ¹⁹FNMR CDCl₃) δ (471 MHz, 7.95-7.83 (m, 1H), 7.79 (dd, J = 8.1, CDCl₃) δ1.7 Hz, 1H), −58.58, 7.52 (d, J = 8.1 Hz, −69.30, 1H), 7.44 (s, 2H),−112.02 6.71 (s, 1H), 6.49 (t, J = 5.7 Hz, 1H), 5.85 (dd, J = 32.5, 9.6Hz, 1H), 4.61 (p, J = 8.9 Hz, 1H), 3.26 (dd, J = 7.3, 5.6 Hz, 2H), 2.45(dt, J = 15.2, 7.5 Hz, 1H), 1.96-1.81 (m, 2H), 1.79-1.61 (m, 2H),1.63-1.52 (m, 2H), 1.16-1.05 (m, 2H), 1.02 (d, J = 6.6 Hz, 2H) F94 615([M − H]⁻) ¹H NMR (400 MHz, ¹⁹F NMR CDCl₃) δ 7.87 (d, J = 1.6 Hz, (471MHz, 1H), CDCl₃) δ 7.80 (dd, J = 8.1, 1.7 Hz, −58.58, 1H), 7.58 (d, J =8.0 Hz, −69.30, 1H), 7.44 (s, 2H), −112.02 6.69 (t, J = 5.3 Hz, 1H),6.65 (s, 1H), 5.86 (dd, J = 32.5, 9.6 Hz, 1H), 4.61 (p, J = 8.9 Hz, 1H),4.04 (dd, J = 5.2, 2.6 Hz, 2H), 2.24 (t, J = 2.6 Hz, 1H), 1.73-1.59 (m,2H), 1.21-1.06 (m, 2H) F95 641 ([M − H]⁻) ¹H NMR (400 MHz, ¹⁹F NMRCDCl₃) δ (471 MHz, 7.97-7.82 (m, 1H), 7.79 (dd, J = 8.1, CDCl₃) δ 1.7Hz, 1H), −58.70, 7.55 (d, J = 8.1 Hz, −69.30, 1H), 7.44 (s, 2H), −111.99(d, J = 32.8 Hz), 6.78 (t, J = 6.3 Hz, −123.08 (dd, 1H), 6.60 (s, 1H), J= 56.0, 6.06-5.55 (m, 2H), 15.5 Hz) 4.61 (p, J = 8.9 Hz, 1H), 3.66 (tdd,J = 15.0, 6.2, 4.0 Hz, 2H), 1.74-1.55 (m, 2H), 1.20-1.08 (m, 2H) F96 673([M − H]⁻) ¹H NMR (400 MHz, ¹⁹F NMR CDCl₃) δ 7.79 (d, J = 1.6 Hz, (471MHz, 1H), CDCl₃) δ 7.71 (dd, J = 8.1, 1.7 Hz, −58.98, 1H), 7.47 (t, J =4.1 Hz, −69.32 (d, J = 8.7 Hz), 2H), 7.43 (s, 2H), −72.64, 5.81 (dd, J =32.6, −111.94 9.6 Hz, 1H), 4.60 (p, J = 8.9 Hz, 1H), 4.11 (m, 2H), 3.27(d, J = 31.4 Hz, 3H), 1.36-1.33 (m, 2H), 1.32-1.28 (m, 2H) F97 639 ([M −H]⁻) ¹H NMR (400 MHz, ¹⁹F NMR CDCl₃) δ 7.69 (d, J = 8.1 Hz, (471 MHz,1H), 7.58 (d, CDCl₃) δ J = 1.7 Hz, 1H), −69.36, 7.51 (dd, J = 8.3, 1.7Hz, −72.58, 1H), 7.42 (s, 2H), −111.68 6.87 (s, 1H), 5.78 (dd, J = 32.5,9.6 Hz, 1H), 4.58 (p, J = 8.8 Hz, 1H), 4.29-4.09 (m, 2H), 3.32 (s, 3H),1.58-1.46 (m, 2H), 1.40-1.30 (m, 2H) F98 661 ([M − H]⁻) ¹H NMR (400 MHz,¹⁹F NMR CDCl₃) δ (471 MHz, 7.86-7.77 (m, 2H), 7.71 (d, J = 8.1 Hz,CDCl₃) δ 1H), 7.50 (d, −59.23, J = 8.0 Hz, 1H), −69.32, 7.44 (s, 2H),−72.55 (d, J = 8.6 Hz), 7.43-7.30 (m, 1H), 5.83 (ddd, J = 32.6,−109.09-−114.80 (m) 9.6, 1.6 Hz, 1H), 4.84 (q, J = 7.2 Hz, 1H), 4.61 (p,J = 8.9 Hz, 1H), 3.85 (tdd, J = 15.0, 9.3, 6.6 Hz, 1H), 3.67 (dtd, J =17.5, 8.9, 4.2 Hz, 1H), 1.87 (dt, J = 14.2, 7.1 Hz, 1H), 1.75 (dt, J =14.1, 7.2 Hz, 1H), 0.94 (t, J = 7.4 Hz, 3H) F99 661 ([M + H]⁺) ¹H NMR(400 MHz, ¹⁹F NMR CDCl₃) δ 7.88 (s, (471 MHz, 1H), 7.80 (dd, J = 8.1,CDCl₃) δ 1.7 Hz, 1H), −60.53, 7.58 (d, J = 8.1 Hz, −69.32 (d, J = 8.5Hz), 1H), 7.45 (s, 2H), rotamers 5.85 (dd, J = 32.6, −69.96 (t, 9.5 Hz,1H), 4.94 (d, J = 8.8 Hz) & J = 16.1 Hz, 1H), −70.49 (t, J = 8.4 Hz),4.63 (p, J = 8.9 Hz, −111.88 (d, J = 33.2 Hz) 1H), 4.28 (d, J = 11.5 Hz,1H), 4.18-3.78 (m, 2H), 3.21 (s, 3H), 2.88 (s, 3H) F100 627 ([M − H]⁻)¹H NMR (400 MHz, ¹⁹F NMR CDCl₃) δ 7.65 (dd, J = 8.2, (471 MHz, 4.5 Hz,1H), CDCl₃) δ 7.60 (dd, J = 3.9, 1.4 Hz, −68.53-−70.20 (m), 1H), 7.50(dt, J = 8.2, −72.49 (d, J = 9.9 Hz), 2.1 Hz, 1H), −110.53-−114.49 (m)7.43 (d, J = 4.4 Hz, 2H), 7.27 (d, J = 2.7 Hz, 1H), 7.09 (dd, J = 8.0,4.4 Hz, 1H), 5.78 (dd, J = 32.5, 9.6 Hz, 1H), 4.87-4.66 (m, 1H),4.69-4.41 (m, 1H), 4.10-3.92 (m, 1H), 3.85 (dtdd, J = 17.8, 8.9, 5.6,3.2 Hz, 1H), 2.05-1.94 (m, 1H), 1.89-1.75 (m, 1H), 1.26 (qd, J = 5.2,4.3, 2.3 Hz, 3H) F101 629 ([M − H]⁻) ¹H NMR (300 MHz, IR (thin film)Methanol-d₄) δ 3289, 3082, 8.07 (d, J = 1.6 Hz, 1H), 2362, 1681,8.06-7.97 (m, 1H), 1643, 1598, 7.80 (d, J = 8.2 Hz, 1552, 1246, 1H),7.78 (s, 2H), 1165, 1118, 6.48 (dd, J = 34.1, 811, 733, 9.8 Hz, 1H),4.96 (q, 672 cm⁻¹ J = 9.2 Hz, 1H), 4.28-4.07 (m, 1H), 3.05-2.80 (m, 2H),2.78-2.46 (m, 2H), 1.63-1.42 (m, 2H), 1.21-1.03 (m, 2H) F102 619 ([M −H]⁻) ¹H NMR (400 MHz, IR (thin film) DMSO-d₆) δ 8.93 (d, 3404, 2929, J =7.6 Hz, 1H), 1664 cm⁻¹ 8.06 (s, 1H), 8.03 (d, J = 8.4 Hz, 1H), 7.58 (d,J = 7.6 Hz, 1H), 7.44 (s, 2H), 6.74 (dd, J = 36.0, 10.0 Hz, 1H),4.98-4.89 (m, 1H), 4.32-4.25 (m, 1H), 4.15-4.09 (m, 2H), 3.28 (s, 3H),2.35 (s, 6H), 1.28 (d, J = 6.8 Hz, 3H) F103 605 ([M − H]⁻) ¹H NMR (400MHz, IR (thin film) DMSO-d₆) δ 8.77 (t, J = 6.0 Hz, 3399, 1661, 1H),1167 cm⁻¹ 8.07 (s, 1H), 8.04 (s, 1H), 7.68 (d, J = 8.0 Hz, 1H), 7.44 (s,2H), 6.75 (dd, J = 36.0, 10.4 Hz, 1H), 4.94-4.89 (m, 1H), 4.22-4.16 (m,4H), 3.14 (s, 3H), 2.32 (s, 6H) F104 675 ([M + H]⁺) ¹H NMR (300 MHz, ¹⁹FNMR CDCl₃) δ 7.86 (s, (376 MHz, 1H), 7.77 (m, 1H), CDCl₃) δ 7.65 (d, J =8.1 Hz, −59.08, 1H), 7.44 (s, 2H), −69.30 (d, J = 2.3 Hz), 6.80 (d, J =5.4 Hz, −69.76, 1H), 5.82 (dd, J = 32.6, −111.87 (dd, 9.6 Hz, 1H), J =4.8, 2.3 Hz) 4.56 (m, 2H), 4.17 (dq, J = 14.9, 8.9 Hz, 1H), 3.92 (dq, J= 15.1, 9.0 Hz, 1H), 3.61 (dt, J = 11.8, 5.7 Hz, 1H), 3.49 (m, 1H), 2.81(m, 1H), 2.04 (m, 2H), 1.68 (m, 1H) F105 590 ([M + H]⁺) ¹H NMR (300 MHz,IR (thin film) DMSO-d₆) δ 8.79 (t, J = 6.0 Hz, 3400, 2929, 1H), 1661,1171 cm⁻¹ 8.12 (s, 1H), 8.08 (d, J = 8.1 Hz, 1H), 7.81 (s, 2H),7.70-7.67 (m, 2H), 6.87 (dd, J = 36.6, 10.5 Hz, 1H), 5.24-5.18 (m, 1H),4.23-4.06 (m, 4H), 2.35 (s, 3H) F106 661 ([M + H]⁺) ¹H NMR (400 MHz, IR(thin film) DMSO-d₆) δ 9.31 (d, 3421, 2925, J = 7.1 Hz, 1H), 1731, 769cm⁻¹ 8.14 (s, 1H), 8.08-8.04 (m, 3H), 7.67 (d, J = 7.6 Hz, 1H), 6.87(dd, J = 36.0, 10.4 Hz, 1H), 5.27-5.22 (m, 1H), 5.10-5.03 (m, 1H),4.71-4.67 (m, 1H), 4.45-4.37 (m, 2H), 4.15-4.11 (m, 1H) F107 88-93 685([M − H]⁻) ¹H NMR (300 MHz, DMSO-d₆) δ 8.89 (t, J = 6.0 Hz, 1H), 8.64(t, J = 6.4 Hz, 1H), 8.11 (s, 1H), 8.08 (d, J = 8.7 Hz, 2H), 7.86 (d, J= 8.4 Hz, 1H), 7.70 (d, J = 8.1 Hz, 1H), 7.62 (d, J = 8.4 Hz, 1H), 6.85(dd, J = 35.7, 9.9 Hz, 1H), 5.19-5.18 (m, 1H), 4.02-3.90 (m, 4H) F108725 ([M − H]⁻) ¹H NMR (300 MHz, IR (thin film) DMSO-d₆) δ 9.26 (br 3429,2925, s, 1H), 8.14 (s, 1H), 1667, 749 cm⁻¹ 8.06 (d, J = 7.2 Hz, 1H),7.96 (s, 2H), 7.91 (s, 1H), 7.58 (d, J = 8.1 Hz, 1H), 6.87 (dd, J =35.4, 9.9 Hz, 1H), 5.22-5.21 (m, 1H), 4.22-4.21 (m, 2H), 3.17 (s, 3H),1.08-1.02 (m, 2H), 0.85-0.81 (m, 2H) F109 655 ([M − H]⁻) ¹H NMR (300MHz, IR (thin film) DMSO-d₆) δ 8.85 (d, 3284, 2923, J = 7.2 Hz, 1H),1641, 845 cm⁻¹ 8.63 (t, J = 6.6 Hz, 1H), 8.11 (s, 1H), 8.06 (d, J = 8.1Hz, 1H), 7.93 (s, 1H), 7.85 (s, 1H), 7.80 (s, 1H), 7.67 (d, J = 8.1 Hz,1H), 6.87 (dd, J = 36.0, 10.2 Hz, 1H), 5.23-5.17 (m, 1H), 4.53-4.48 (m,1H), 4.01-3.86 (m, 2H), 1.28 (d, J = 6.0 Hz, 3H) F110 677 ([M + H]⁺) ¹HNMR (400 MHz, IR (thin film) DMSO-d₆) δ 8.89 (t, J = 6.0 Hz, 3330, 2927,1H), 1660, 1163, 8.63 (t, J = 6.4 Hz, 1H), 670 cm⁻¹ 8.11-8.00 (m, 4H),7.71 (d, J = 8.4 Hz, 1H), 6.84 (dd, J = 36.0, 10.4 Hz, 1H), 5.25-5.21(m, 1H), 3.98-3.91 (m, 4H) F111 78-80 665 ([M − H]⁻) ¹H NMR (400 MHz,CDCl₃) δ 7.84 (s, 1H) 7.79 (d, J = 8.0 Hz, 1H), 7.54 (d, J = 7.6 Hz,1H), 7.41 (s, 1H), 7.36 (s, 1H), 6.72-6.64 (dd, J = 17.6, 12.0 Hz, 1H),6.38 (br s, 1H), 5.88-5.74 (m, 2H), 4.61-4.56 (m, 1H), 4.22-4.15 (m,2H), 3.33 (s, 3H), 1.25-1.17 (m, 3H), 0.89-0.86 (m, 1H) F112 607 ([M −H]⁻) ¹H NMR (400 MHz, ¹⁹F NMR CDCl₃) δ 7.83 (d, J = 1.7 Hz, (376 MHz,1H), CDCl₃) δ 7.73 (dd, J = 8.1, 1.8 Hz, −59.16, 1H), 7.52 (d, J = 8.0Hz, −72.60, 1H), 7.49 (d, J = 2.1 Hz, −92.33-−97.71 (m), 1H), 7.45 (d,−115.49; J = 8.3 Hz, 1H), IR (thin film) 7.24 (dd, J = 8.4, 2.1 Hz,3286, 1647, 1H), 7.18 (t, J = 6.5 Hz, 1543 cm⁻¹ 1H), 6.63 (d, J = 7.7Hz, 1H), 5.94 (dd, J = 33.9, 9.8 Hz, 1H), 4.84 (p, J = 7.1 Hz, 1H), 4.31(ddd, J = 15.8, 13.1, 9.7 Hz, 1H), 3.89 (qdd, J = 8.8, 6.4, 2.0 Hz, 2H),1.68-1.55 (m, 3H), 1.51 (d, J = 7.0 Hz, 3H) F113 652 ([M + H]⁺) ¹H NMR(300 MHz, IR (thin film) CDCl₃) δ 7.89 (s, 3382, 2925, 1H), 7.83 (d, J =8.4 Hz, 1673, 1160 1H), 7.58 (d, J = 8.4 Hz, 764 cm⁻¹ 1H), 7.41 (s, 1H),7.37 (s, 1H), 6.71-6.63 (m, 1H), 6.38 (br s, 1H), 5.93-5.74 (m, 2H),4.63-4.57 (m, 1H), 4.02-3.86 (m, 2H), 1.19-1.17 (m, 2H), 0.90-0.86 (m,2H) F114 657 ([M + H]⁺) ¹H NMR (400 MHz, IR (thin film) DMSO-d₆) δ 9.30(br 3437, 2924, s, 1H), 8.13 (s, 1H), 1667, 750 cm⁻¹ 8.05 (d, J = 8.0Hz, 1H), 8.00 (d, J = 6.0 Hz, 2H), 7.59 (d, J = 8.7 Hz, 1H), 6.84 (dd, J= 35.6, 10.0 Hz, 1H), 5.24-5.23 (m, 1H), 4.21-4.10 (m, 2H), 3.18 (s,3H), 1.04-1.01 (m, 2H), 0.86-0.83 (m, 2H) F115 639 ([M + H]⁺) ¹H NMR(300 MHz, IR (thin film) DMSO-d₆) δ 9.26 (s, 3430, 2925, 1H), 8.14 (s,1H), 1668, 749 cm⁻¹ 8.06 (d, J = 8.4 Hz, 1H), 7.80 (s, 2H), 7.69 (s,1H), 7.59 (d, J = 8.1 Hz, 1H), 6.87 (dd, J = 35.4, 9.9 Hz, 1H),5.24-5.17 (m, 1H), 4.22 (br s, 2H), 3.17 (s, 3H), 1.08-1.00 (m, 2H),0.85-0.83 (m, 2H) F116 667 ([M − H]⁻) ¹H NMR (300 MHz, IR (thin film)DMSO-d₆) δ 9.10 (br 3421, 2925, s, 1H), 1667, 1166, 8.17-8.07 (m, 3H),8.02 (d, J = 8.1 Hz, 750 cm⁻¹ 1H), 7.93 (s, 1H), 7.84 (s, 1H), 7.80-7.79(m, 1H), 6.87 (dd, J = 36.0, 9.9 Hz, 1H), 5.23-5.17 (m, 1H), 3.96-3.87(m, 2H), 1.40-1.25 (m, 2H), 1.03-0.99 (m, 2H) F117 717 ([M + H]⁺) ¹H NMR(400 MHz, IR (thin film) DMSO-d₆) δ 9.26 (s, 3429, 2920, 1H), 8.13 (s,1H), 1260, 750 cm⁻¹ 8.06-7.99 (m, 3H), 7.59 (d, J = 8.0 Hz, 1H), 6.85(dd, J = 36.0, 10.4 Hz, 1H), 5.25-5.20 (m, 1H), 4.20-4.18 (m, 2H), 3.18(s, 3H), 1.28-1.23 (m, 2H), 1.03-0.99 (m, 2H) F118 761 ([M + H]⁺) ¹H NMR(300 MHz, IR (thin film) DMSO-d₆) δ 9.26 (br 3442, 2931, s, 1H), 1667,748 cm⁻¹ 8.17-8.14 (m, 2H), 8.06 (d, J = 8.1 Hz, 1H), 7.95 (s, 1H), 7.59(d, J = 8.1 Hz, 1H), 6.87 (dd, J = 35.4, 9.3 Hz, 1H), 5.25-5.19 (m, 1H),4.20-4.18 (m, 2H), 3.19 (s, 3H), 1.28-1.26 (m, 2H), 1.04-1.00 (m, 2H)F119 633 ([M + H]⁺) ¹H NMR (300 MHz, IR (thin film) DMSO-d₆) δ 9.27 (s,3436, 2925, 1H), 8.11 (s, 1H), 1637, 750 cm⁻¹ 8.05 (d, J = 8.1 Hz, 1H),7.59 (d, J = 8.1 Hz, 1H), 7.44 (s, 2H), 6.87 (dd, J = 36.0, 10.2 Hz,1H), 4.96-4.92 (m, 1H), 4.22-4.20 (m, 2H), 3.17 (s, 3H), 2.35 (s, 6H),1.20-0.98 (m, 2H), 0.82-0.79 (m, 2H) F120 640 ([M + H]⁺) ¹H NMR (300MHz, IR (thin film) DMSO-d₆) δ 9.24 (s, 3444, 2926, 1H), 8.14 (s, 1H),1667, 1261 cm⁻¹ 8.06 (d, J = 8.4 Hz, 1H), 7.99 (s, 1H), 7.75 (d, J = 8.4Hz, 1H), 7.67 (d, J = 8.4 Hz, 1H), 7.58 (d, J = 8.1 Hz, 1H), 6.86 (dd, J= 36.0, 9.9 Hz, 1H), 5.21-5.15 (m, 1H), 4.23 (br s, 2H), 3.18 (s, 3H),1.04-1.00 (m, 2H), 0.93-0.79 (m, 2H) F121 655 ([M − H]⁻) ¹H NMR (300MHz, IR (thin film) DMSO-d₆) δ 8.85 (d, 3284, 2923, J = 7.2 Hz, 1H),1641, 845 cm⁻¹ 8.63 (t, J = 6.6 Hz, 1H), 8.11 (s, 1H), 8.06 (d, J = 8.1Hz, 1H), 7.93 (s, 1H), 7.85 (s, 1H), 7.80 (s, 1H), 7.67 (d, J = 8.1 Hz,1H), 6.87 (dd, J = 36.0, 10.2 Hz, 1H), 5.23-5.17 (m, 1H), 4.53-4.48 (m,1H), 4.01-3.86 (m, 2H), 1.28 (d, J = 6.0 Hz, 3H) F122 643 ([M + H]⁺) ¹HNMR (300 MHz, IR (thin film) DMSO-d₆) δ 8.73 (t, J = 6.0 Hz, 3360, 2925,1H), 1657, 1163 cm⁻¹ 8.63 (t, J = 6.0 Hz, 1H), 8.12 (s, 1H), 8.08 (d, J= 8.1 Hz, 1H), 7.93 (s, 1H), 7.85 (s, 1H), 7.80-7.79 (m, 1H), 7.71 (d, J= 8.1 Hz, 1H), 6.87 (dd, J = 35.7, 10.2 Hz, 1H), 5.20-5.17 (m, 1H),4.04-3.90 (m, 4H) F123 ¹H NMR (400 MHz, ¹⁹F NMR CDCl₃) δ 7.74 (d, J =1.5 Hz, (376 MHz, 1H), CDCl₃) δ 7.57-7.39 (m, 4H), −69.48 (d, J = 2.4Hz), 7.27-7.18 (m, 2H), −72.40, 7.03 (d, J = 7.6 Hz, 1H), −112.78 5.79(dd, J = 32.8, 9.7 Hz, 1H), 4.88 (p, J = 7.1 Hz, 1H), 4.59 (dddt, J =18.9, 14.3, 9.9, 4.9 Hz, 1H), 3.89 (qdd, J = 8.9, 6.3, 1.9 Hz, 2H), 1.54(d, J = 7.0 Hz, 3H) F124 ¹H NMR (400 MHz, ¹⁹F NMR CDCl₃) δ 7.77 (d, J =1.2 Hz, (376 MHz, 1H), CDCl₃) δ 7.59-7.35 (m, 6H), −69.47 (d, J = 2.3Hz), 7.31-7.18 (m, 1H), −72.33, 5.80 (dd, J = 32.8, 9.7 Hz, −112.79 1H),4.61 (p, J = 9.1 Hz, 1H), 4.26 (d, J = 5.2 Hz, 2H), 4.01-3.85 (m, 2H)F125 ¹H NMR (400 MHz, ¹⁹F NMR CDCl₃) δ 7.75 (d, J = 1.7 Hz, (376 MHz,1H), CDCl₃) δ 7.60-7.37 (m, 4H), −69.49 (d, J = 2.3 Hz), 7.32-7.18 (m,2H), −72.61, 7.10 (t, J = 6.5 Hz, 1H), −112.79 5.81 (dd, J = 32.8, 9.6Hz, 1H), 4.61 (p, J = 8.9 Hz, 1H), 4.02-3.76 (m, 2H), 1.45 (q, J = 4.2Hz, 2H), 0.88 (q, J = 4.2 Hz, 2H) F126 579 ([M − H]⁻) ¹H NMR (500 MHz,¹⁹F NMR CDCl₃) δ 7.82 (d, J = 1.8 Hz, (471 MHz, 1H), CDCl₃) δ 7.76-7.67(m, 1H), −59.29, 7.53 (d, J = 8.1 Hz, 1H), −69.36 (t, J = 7.3 Hz), 7.44(s, 2H), −112.12 (dd, 7.13-7.03 (m, 1H), J = 32.7, 8.2 Hz) 6.84 (s, 1H),6.06 (s, 1H), 5.83 (dd, J = 32.6, 9.6 Hz, 1H), 4.72 (dt, J = 7.8, 6.6Hz, 1H), 4.60 (p, J = 8.9 Hz, 1H), 1.93 (ddd, J = 13.8, 7.6, 6.2 Hz,1H), 1.77 (dp, J = 14.4, 7.3 Hz, 1H), 0.98 (t, J = 7.4 Hz, 3H) F127 551([M − H]⁻) ¹H NMR (500 MHz, ¹⁹F NMR CDCl₃) δ (471 MHz, 7.89-7.85 (m,1H), 7.78 (dd, J = 8.1, CDCl₃) δ 1.8 Hz, 1H), −59.28, 7.62 (d, J = 8.1Hz, −69.31 (d, J = 8.4 Hz), 1H), 7.44 (s, 2H), −111.99 (d, J = 32.4 Hz)6.78 (t, J = 4.7 Hz, 1H), 6.22 (s, 1H), 5.83 (dd, J = 32.5, 9.6 Hz, 1H),5.68-5.58 (m, 1H), 4.61 (p, J = 8.9 Hz, 1H), 4.20 (s, 1H), 4.19 (s, 1H)F128 622 ([M + H]⁺) ¹H NMR (400 MHz, ¹⁹F NMR CDCl₃) δ 7.87 (s, (376 MHz,1H), 7.78 (d, J = 7.4 Hz, CDCl₃) δ 1H), 7.53 (d, J = 7.9 Hz, −58.69,1H), −72.64, 7.50-7.42 (m, 2H), −92.07-−98.57 (m), 7.23 (d, J = 9.1 Hz,1H), −115.55 6.92 (s, 1H), 6.32 (s, 1H), 5.96 (dd, J = 3.39 9.7 Hz, 1H),4.37-4.25 (m, 1H), 3.94 (ddd, J = 18.3, 9.1, 6.5 Hz, 2H), 1.61 (t, J =18.5 Hz, 3H), 1.25-1.18 (m, 2H), 1.03-0.94 (m, 1H), 0.92-0.84 (m, 1H)F129 596 ([M + H]⁺) ¹H NMR (400 MHz, ¹⁹F NMR CDCl₃) δ 7.86 (d, J = 1.6Hz, (376 MHz, 1H), CDCl₃) δ 7.77 (dd, J = 8.1, 1.6 Hz, 59.21, 1H), 7.59(d, J = 8.1 Hz, −72.54, 1H), 7.49 (d, J = 2.1 Hz, −92.43-−97.26 (m),1H), 7.45 (d, −115.50 J = 8.3 Hz, 1H), 7.24 (dd, J = 8.4, 2.1 Hz, 1H),6.70 (d, J = 5.8 Hz, 1H), 6.61 (t, J = 5.3 Hz, 1H), 5.95 (dd, J = 34.0,9.8 Hz, 1H), 4.31 (ddd, J = 15.8, 13.1, 9.8 Hz, 1H), 4.22 (dd, J = 5.4,2.4 Hz, 2H), 4.01-3.88 (m, 2H), 1.62 (t, J = 18.4 Hz, 3H) F130 727 ([M +H]⁺) ¹H NMR (400 MHz, IR (thin film) DMSO-d₆) δ 9.26 (br 3435, 2926, s,1H), 8.14 (s, 1H), 1667, 749 cm⁻¹ 8.09 (s, 1H), 8.05 (d, J = 8.0 Hz,1H), 7.85 (s, 1H), 7.61-7.56 (m, 2H), 6.84 (dd, J = 36.0, 10.0 Hz, 1H),5.18-5.13 (m, 1H), 4.22-4.21 (m, 2H), 3.17 (s, 3H), 1.04-1.02 (m, 2H),0.85-0.83 (m, 2H) F131 609 ([M + H]⁺) ¹H NMR (400 MHz, IR (thin film)DMSO-d₆) δ 9.10 (s, 3458, 2926, 1H), 8.63 (t, J = 8.4 Hz, 1671, 1167cm⁻¹ 1H), 8.15-8.11 (m, 2H), 8.09 (d, J = 9.2 Hz, 1H), 7.99-7.94 (m,1H), 7.51 (d, J = 9.2 Hz, 1H), 7.69 (s, 1H), 6.84 (dd, J = 36.0, 10.0Hz, 1H), 5.18-5.14 (m, 1H), 3.95-3.91 (m, 2H), 1.03-1.01 (m, 2H),0.85-0.81 (m, 2H) F132 595 ([M − H]⁻) ¹H NMR (400 MHz, IR (thin film)DMSO-d₆) δ 8.84 (d, 3428, 2925, J = 7.2 Hz, 1H), 1650, 1167 cm⁻¹ 8.64(t, J = 6.4 Hz, 1H), 8.10 (s, 1H), 8.05 (d, J = 8.0 Hz, 1H), 7.97 (d, J= 6.4 Hz, 1H), 7.68-7.64 (m, 2H), 7.53-7.48 (m, 1H), 6.83 (dd, J = 36.0,10.4 Hz, 1H), 5.18-5.13 (m, 1H), 4.52-4.49 (m, 1H), 3.99-3.87 (m, 2H),1.30 (d, J = 7.2 Hz, 3H) F133 639 ([M + H]⁺) ¹H NMR (300 MHz, IR (thinfilm) DMSO-d₆) δ 9.26 (s, 3430, 2925, 1H), 8.14 (s, 1H), 1668, 749 cm⁻¹8.06 (d, J = 8.4 Hz, 1H), 7.80 (s, 2H), 7.69 (s, 1H), 7.59 (d, J = 8.1Hz, 1H), 6.87 (dd, J = 35.4, 9.9 Hz, 1H), 5.24-5.17 (m, 1H), 4.22 (br s,2H), 3.17 (s, 3H), 1.08-1.00 (m, 2H), 0.85-0.83 (m, 2H) F134 633 ([M +H]⁺) ¹H NMR (300 MHz, IR (thin film) DMSO-d₆) δ 9.27 (s, 3436, 2925,1H), 8.11 (s, 1H), 1637, 750 cm⁻¹ 8.05 (d, J = 8.1 Hz, 1H), 7.59 (d, J =8.1 Hz, 1H), 7.44 (s, 2H), 6.87 (dd, J = 36.0, 10.2 Hz, 1H), 4.96-4.92(m, 1H), 4.22-4.20 (m, 2H), 3.17 (s, 3H), 2.35 (s, 6H), 1.20-0.98 (m,2H), 0.82-0.79 (m, 2H) F135 640 ([M + H]⁺) ¹H NMR (300 MHz, IR (thinfilm) DMSO-d₆) δ 9.24 (s, 3444, 2926, 1H), 8.14 (s, 1H), 1667, 1261 cm⁻¹8.06 (d, J = 8.4 Hz, 1H), 7.99 (s, 1H), 7.75 (d, J = 8.4 Hz, 1H), 7.67(d, J = 8.4 Hz, 1H), 7.58 (d, J = 8.1 Hz, 1H), 6.86 (dd, J = 36.0, 9.9Hz, 1H), 5.21-5.15 (m, 1H), 4.23 (br s, 2H), 3.18 (s, 3H), 1.04-1.00 (m,2H), 0.93-0.79 (m, 2H) F136 609 ([M + H]⁺) ¹H NMR (400 MHz, IR (thinfilm) DMSO-d₆) δ 9.10 (s, 3431, 2925, 1H), 8.17 (t, J = 7.4 Hz, 1650cm⁻¹ 1H), 8.11 (s, 1H), 8.08 (d, J = 7.6 Hz, 1H), 8.02 (d, J = 8.0 Hz,1H), 7.80 (d, J = 10.4 Hz, 1H), 7.71 (d, J = 8.4 Hz, 1H), 7.55 (d, J =8.4 Hz, 1H), 6.81 (dd, J = 35.6, 9.6 Hz, 1H), 5.20-5.15 (m, 1H),3.95-3.91 (m, 2H), 1.23-1.08 (m, 2H), 0.86-0.81 (m, 2H) F137 657 ([M +H]⁺) ¹H NMR (400 MHz, IR (thin film) DMSO-d₆) δ 8.79 (t, J = 5.6 Hz,3412, 2924, 1H), 1660, 1260, 8.12 (br s, 1H), 8.08 (d, J = 7.6 Hz, 750cm⁻¹ 1H), 7.93 (s, 1H), 7.85 (s, 1H), 7.79 (s, 1H), 7.69 (d, J = 8.0 Hz,1H), 6.85 (dd, J = 35.6, 9.6 Hz, 1H), 5.23-5.18 (m, 1H), 4.22-4.16 (m,4H), 3.14 (s, 3H) F138 657 ([M + H]⁺) ¹H NMR (300 MHz, IR (thin film)DMSO-d₆) δ 8.83 (d, 3310, 1653, J = 7.8 Hz, 1H), 1169 cm⁻¹ 8.62 (t, J =6.0 Hz, 1H), 8.12-8.03 (m, 3H), 7.71-7.64 (m, 3H), 6.85 (dd, J = 36.0,9.9 Hz, 1H), 5.20-5.14 (m, 1H), 4.53-4.48 (m, 1H), 4.01-3.89 (m, 2H),1.30 (d, J = 7.2 Hz, 3H) F139 669 ([M + H]⁺) ¹H NMR (400 MHz, IR (thinfilm) DMSO-d₆) δ 9.10 (s, 3459, 1667, 1H), 8.16-8.00 (m, 1165 cm⁻¹ 5H),7.71 (s, 2H), 6.84 (dd, J = 36.0, 10.0 Hz, 1H), 5.20-5.16 (m, 1H),3.95-3.91 (m, 2H), 1.38-1.33 (m, 2H), 1.08-1.02 (m, 2H) F140 659 ([M +H]⁺) ¹H NMR (300 MHz, IR (thin film) CDCl₃) δ 7.86 (s, 3431, 2922, 1H),7.79 (d, J = 9.0 Hz, 1663, 1260, 1H), 749 cm⁻¹ 7.61-7.60 (m, 1H), 7.45(s, 2H), 6.94-6.87 (m, 1H), 6.48 (d, J = 15.6 Hz, 1H), 5.89 (dd, J = 9.6Hz, 32.4 Hz, 1H), 5.05-5.00 (m, 1H), 4.63-4.60 (m, 1H), 3.11-3.05 (m,2H), 1.49 (d, J = 7.2 Hz, 3H) F141 631 ([M + H]⁺) ¹H NMR (300 MHz, IR(thin film) DMSO-d₆) δ 8.84 (d, 3281, 3098, J = 7.8 Hz, 1H), 1644 cm⁻¹8.65 (t, J = 6.3 Hz, 1H), 8.10 (s, 2H), 8.06 (d, J = 8.1 Hz, 2H),7.67-7.60 (m, 2H), 6.91 (dd, J = 9.9, 36.0 Hz, 1H), 5.35-5.28 (m, 1H),4.53-4.48 (m, 1H), 4.02-3.86 (m, 2H), 1.30 (d, J = 6.9 Hz, 3H) F142 661([M + H]⁻) ¹H NMR (300 MHz, IR (thin film) DMSO-d₆) δ 8.85 (d, 1731,1267, J = 9.0 Hz 1H), 1049 cm⁻¹ 8.63 (t, J = 6.0 Hz, 1H), 8.13 (s, 1H),8.09-8.00 (m, 4H), 7.65 (t, J = 8.1 Hz, 1H), 6.88-6.72 (m, 1H),5.37-5.24 (m, 1H), 4.51 (t, J = 9.0 Hz, 1H), 4.05-3.84 (m, 2H), 1.29 (d,J = 6.0 Hz, 3H) F143 677 ([M + H]⁺) ¹H NMR (300 MHz, IR(thin film)DMSO-d₆) δ 9.30 (d, 1732, 1266, J = 9.3 Hz, 1H), 1173, 1049 cm⁻¹ 8.14(s, 1H), 8.07 (d, J = 6.0 Hz, 1H), 8.02 (br s, 2H), 7.67 (d, J = 8.1 Hz,1H), 7.44 (t, J = 52.2 Hz, 1H), 6.89-6.74 (m, 1H), 5.30 (t, J = 9.0 Hz,1H), 5.11-5.02 (m, 1H), 4.77 (t, J = 9.0 Hz, 1H), 4.43-4.33 (m, 2H),4.13 (t, J = 6.3 Hz, 1H) F144 613 ([M + H]⁺) ¹H NMR (300 MHz, IR (thinfilm) CDCl₃) δ 7.86 (s, 3462, 1682, 1H), 7.79 (d, J = 8.0 Hz, 1116 cm⁻¹1H), 7.58 (d, J = 8.0 Hz, 1H), 7.49 (s, 1H), 7.47 (s, 1H), 7.26-7.21 (m,1H), 6.64-6.60 (m, 1H), 6.33 (d, J = 7.6 Hz, 1H), 5.91 (dd, J = 9.6,32.0 Hz, 1H), 4.73-4.61 (m, 1H), 4.20-4.15 (m, 1H), 3.98-3.90 (m, 2H),1.33-1.28 (m, 3H) F145 717 ([M + H]⁺) ¹H NMR (400 MHz, IR (thin film)DMSO-d₆) δ 9.26 (s, 3429, 2920, 1H), 8.13 (s, 1H), 1260, 750 cm⁻¹8.06-7.99 (m, 3H), 7.59 (d, J = 8.0 Hz, 1H), 6.85 (dd, J = 10.4, 36.0Hz, 1H), 5.25-5.20 (m, 1H), 4.20-4.18 (m, 2H), 3.18 (s, 3H), 1.28-1.23(m, 2H), 1.03-0.99 (m, 2H) F146 653 ([M + H]⁺) ¹H NMR (400 MHz, IR (thinfilm) DMSO-d₆) δ 8.84 (d, 3429, 2998, J = 8.0 Hz, 1H), 1660, 1030 cm⁻¹8.63 (t, J = 6.4 Hz, 1H), 8.11 (s, 1H), 8.06 (d, J = 8.4 Hz, 1H),7.84-7.81 (m, 2H), 7.68 (d, J = 5.6 Hz, 1H), 6.84 (dd, J = 10.0, 36.0Hz, 1H), 5.92-5.83 (m, 1H), 5.19-5.15 (m, 1H), 5.09 (d, J = 8.4 Hz, 1H),4.98 (d, J = 17.2 Hz, 1H), 4.54-4.47 (m, 1H), 4.03-3.85 (m, 2H), 3.64(d, J = 6.0 Hz, 2H), 1.30 (d, J = 7.6 Hz, 3H) F147 653 ([M + H]⁺) ¹H NMR(400 MHz, IR (thin film) DMSO-d₆) δ 8.84 (d, 3307, 2925, J = 8.0 Hz,1H), 1660, 1117, 8.63 (t, J = 6.4 Hz, 1H), 672 cm⁻¹ 8.12 (s, 1H), 8.06(d, J = 6.4 Hz, 1H), 7.87-7.81 (m, 2H), 7.67 (d, J = 8.4 Hz, 1H), 6.86(dd, J = 10.0, 36.0 Hz, 1H), 6.34-6.19 (m, 1H), 6.07-6.01 (m, 1H),5.22-5.15 (m, 1H), 4.55-4.47 (m, 1H), 4.03-3.85 (m, 2H), 1.51-1.49 (m,3H), 1.30 (d, J = 6.8 Hz, 3H) F148 653 ([M + H]⁺) ¹H NMR (300 MHz, IR(thin film) DMSO-d₆) δ 8.88 (d, 3435, 2999, J = 7.5 Hz, 1H), 1660, 1027cm⁻¹ 8.65 (t, J = 6.3 Hz, 1H), 8.12 (s, 1H), 8.06 (d, J = 8.4 Hz, 1H),7.86 (s, 2H), 7.67 (d, J = 8.1 Hz, 1H), 6.88 (dd, J = 9.9, 35.7 Hz, 1H),5.43 (s, 1H), 5.23-5.17 (m, 1H), 4.93 (s, 1H), 4.53-4.48 (m, 1H),4.04-3.86 (m, 2H), 1.97 (s, 3H), 1.30 (d, J = 6.9 Hz, 3H) F150 645 ([M +H]⁺) ¹H NMR (300 MHz, IR (thin film) DMSO-d₆) δ 9.31 (d, 3854, 3418, J =7.8 Hz, 1H), 2926, 2350, 8.14 (s, 2H), 8.08 (d, J = 7.8 Hz, 1641 cm⁻¹2H), 7.67-7.60 (m, 2H), 6.93 (dd, J = 10.8, 35.6 Hz, 1H), 5.35-5.29 (m,1H), 5.11-5.09 (m, 1H), 4.70-4.66 (m, 1H), 4.66-4.36 (m, 2H), 4.16-4.10(m, 1H) F153 601 ([M + H]⁺) ¹H NMR (300 MHz, IR (thin film) DMSO-d₆) δ8.87 (t, J = 6.0 Hz, 3306, 1661, 1H), 1166, 750 cm⁻¹ 8.62 (t, J = 6.3Hz, 1H), 8.11 (s, 1H), 8.07 (d, J = 8.1 Hz, 1H), 7.91-7.85 (m, 2H), 7.72(d, J = 8.1 Hz, 1H), 6.83 (dd, J = 9.9, 35.7 Hz, 1H), 5.24-5.18 (m, 1H),4.04-3.87 (m, 4H) F154 615 ([M + H]⁺) ¹H NMR (300 MHz, IR (thin film)DMSO-d₆) δ 8.83 (d, 3422, 2928, J = 7.8 Hz, 1H), 1651, 750 cm⁻¹ 8.61 (t,J = 6.0 Hz, 1H), 8.08-8.00 (m, 2H), 7.89-7.83 (m, 2H), 7.66 (d, J = 7.8Hz, 1H), 6.81 (dd, J = 10.5, 36.0 Hz, 1H), 5.22-5.15 (m, 1H), 4.52-4.47(m, 1H), 4.01-3.84 (m, 2H), 1.28 (d, J = 7.5 Hz, 3H) F155 613 ([M + H]⁺)¹H NMR (300 MHz, IR (thin film) DMSO-d₆) δ 9.32 (d, 1674, 1171 cm⁻¹ J =8.1 Hz, 1H), 8.14 (s, 1H), 8.07 (d, J = 8.1 Hz, 1H), 7.77-7.72 (m, 2H),7.68 (d, J = 8.1 Hz, 1H), 6.83 (dd, J = 9.9, 35.7 Hz, 1H), 5.22-5.16 (m,1H), 5.11-5.02 (m, 1H), 4.72-4.66 (m, 1H), 4.44-4.33 (m, 2H), 4.16-4.10(m, 1H) F157 583 ([M + H]⁺) ¹H NMR (300 MHz, IR (thin film) DMSO-d₆) δ8.87 (t, J = 5.7 Hz, 3309, 1697, 1H), 750 cm⁻¹ 8.62 (t, J = 6.0 Hz, 1H),8.12 (s, 1H), 8.08 (d, J = 7.8 Hz, 1H), 7.71-7.60 (m, 3H), 7.52 (d, J =8.4 Hz, 1H), 6.85 (dd, J = 9.9, 36.0 Hz, 1H), 5.24-5.17 (m, 1H),4.02-3.82 (m, 4H) F158 595 ([M + H]⁺) ¹H NMR (300 MHz, IR (thin film)DMSO-d₆) δ 8.88 (t, J = 6.0 Hz, 3306, 2925, 1H), 1661, 1166, 8.63 (t, J= 6.0 Hz, 750 cm⁻¹ 1H), 8.11 (s, 1H), 8.07 (d, J = 7.5 Hz, 1H), 7.76 (s,1H), 7.70 (d, J = 8.1 Hz, 1H), 7.59 (d, J = 9.0 Hz, 1H), 7.21 (d, J =8.4 Hz, 1H), 6.84 (dd, J = 10.2, 36.3 Hz, 1H), 5.04-4.98 (m, 1H),4.02-3.92 (m, 4H), 3.87 (s, 3H) F159 599 ([M + H]⁺) ¹H NMR (400 MHz, IR(thin film) DMSO-d₆) δ 8.84 (d, 3291, 1651, J = 8.0 Hz, 1H), 1168, 673cm⁻¹ 8.63 (t, J = 6.4 Hz, 1H), 8.10 (s, 1H), 8.04 (d, J = 8.4 Hz, 1H),7.76-7.73 (m, 2H), 7.68 (d, J = 8.0 Hz, 1H), 6.78 (dd, J = 9.6, 35.6 Hz,1H), 5.23-5.14 (m, 1H), 4.55-4.53 (m, 1H), 4.03-3.83 (m, 2H), 1.30 (d, J= 7.2 Hz, 3H) F160 585 ([M + H]⁺) ¹H NMR (300 MHz, IR (thin film)DMSO-d₆) δ 8.87 (t, J = 5.7 Hz, 1H), 3303, 1667, 8.62 (t, J = 6.3 Hz,1H), 1166, 749 cm⁻¹ 8.11-8.04 (m, 2H), 7.77-7.66 (m, 3H), 6.81 (dd, J =10.2, 36.0 Hz, 1H), 5.22-5.16 (m, 1H), 4.02-3.92 (m, 4H) F161 609 ([M +H]⁺) ¹H NMR (300 MHz, IR (thin film) DMSO-d₆) δ 8.84 (d, 3421, 2924, J =7.5 Hz, 1H), 1650, 1260 cm⁻¹ 8.64 (t, J = 6.0 Hz, 1H), 8.10 (s, 1H),8.05 (d, J = 9.0 Hz, 1H), 7.75 (s, 1H), 7.66 (d, J = 8.1 Hz, 1H), 7,59(d, J = 7.8 Hz, 1H), 7.21 (d, J = 8.7 Hz, 1H), 6.83 (dd, J = 9.9, 35.7Hz, 1H), 5.04-4.98 (m, 1H), 4.53-4.48 (m, 1H), 4.04-3.92 (m, 2H), 3.87(s, 3H), 1.30 (d, J = 7.2 Hz, 3H) F162 677 ([M + H]⁺) ¹H NMR (300 MHz,IR (thin film) DMSO-d₆) δ 8.84 (d, 3297, 2925, J = 7.2 Hz, 1H), 1656,1167, 8.63 (t, J = 5.7 Hz, 1H), 750 cm⁻¹ 8.10 (s, 1H), 8.05 (d, J = 7.8Hz, 1H), 7.83 (s, 1H), 7.67-7.61 (m, 2H), 7.35 (d, J = 8.4 Hz, 1H), 6.84(dd, J = 10.2, 36,0 Hz, 1H), 5.09-5.03 (m, 1H), 4.94-4.85 (m, 2H),4.53-4.48 (m, 1H), 4.04-3.80 (m, 2H), 1.30 (d, J = 6.9 Hz, 3H) F163 607([M + H]⁺) ¹H NMR (300 MHz, IR (thin film) DMSO-d₆) δ 8.75 (t, J = 6.0Hz, 3422, 1671, 1H), 842 cm⁻¹ 8.14 (t, J = 5.7 Hz, 1H), 7.94 (s, 1H),7.90 (d, J = 7.5 Hz, 1H), 7.80 (s, 2H), 7.61 (d, J = 7.8 Hz, 1H), 7.06(dd, J = 9.9, 36.0 Hz, 1H), 4.30-4.27 (m, 1H), 3.97-3.88 (m, 4H), 2,08(s, 3H) F164 607 ([M + H]⁺) ¹H NMR (300 MHz, IR (thin film) DMSO-d₆) δ8.84 (d, 3425, 2925, J = 7.2 Hz, 1H), 1651, 1275, 8.64 (t, J = 6.3 Hz,1H), 750 cm⁻¹ 8.10 (s, 1H), 8.06 (d, J = 8.4 Hz, 1H), 7.73 (s, 1H), 7.66(d, J = 8.1 Hz, 1H), 7.56 (d, J = 8.4 Hz, 1H), 7.42 (d, J = 8.1 Hz, 1H),6.84 (dd, J = 9.9, 36.0 Hz, 1H), 5.08-5.02 (m, 1H), 4.53-4.48 (m, 1H),3.99-3.85 (m, 2H), 2.74-2.66 (m, 2H), 1.30 (d, J = 7.2 Hz, 3H), 1.19 (t,J = 7.2 Hz, 3H) F165 593 ([M + H]⁺) ¹H NMR (300 MHz, IR (thin film)DMSO-d₆) δ 8.89 (t, J = 6.3 Hz, 3386, 2926, 1H), 1657, 750 cm⁻¹ 8.64 (t,J = 6.6 Hz, 1H), 8.11 (s, 1H), 8.08 (d, J = 8.1 Hz, 1H), 7.73 (s, 1H),7.70 (d, J = 8.1 Hz, 1H), 7.56 (d, J = 7.8 Hz, 1H), 7.42 (d, J = 7.8 Hz,1H), 6.85 (dd, J = 9.9, 36.0 Hz, 1H), 5.09-5.02 (m, 1H), 4.02-3.90 (m,4H), 2.74-2.67 (m, 2H), 1.17 (t, J = 7.5 Hz, 3H) F166 648 ([M + H]⁺) ¹HNMR (400 MHz, ¹⁹F NMR CDCl₃) δ 7.88 (d, J = 1.7 Hz, (376 MHz, 1H),CDCl₃) δ 7.80 (dd, J = 8.1, 1.7 Hz, −59.30, 1H), 7.61 (d, J = 8.1 Hz,−69.32, 1H), 7.44 (s, 2H), −75.38, 6.84 (d, J = 9.6 Hz, −111.93; 1H),5.84 (dd, J = 32.5, IR (thin film) 9.6 Hz, 1H), 1667, 1258, 5.26-5.10(m, 1H), 1208, 1173, 4.68-4.50 (m, 1H), 1118, 807, 3.75 (s, 3H), 666cm⁻¹ 2.92-2.69 (m, 2H) F167 661 ([M + H]⁺) ¹H NMR (500 MHz, IR (thinfilm) CDCl₃) δ 7.87 (d, J = 1.6 Hz, 1654, 1141, 1H), 1118 cm⁻¹ 7.78 (dd,J = 8.1, 1.7 Hz, 1H), 7.64 (d, J = 8.0 Hz, 1H), 7.44 (s, 2H), 6.92 (t, J= 4.2 Hz, 1H), 5.83 (dd, J = 32.5, 9.6 Hz, 1H), 4.61 (p, J = 8.9 Hz,1H), major rotamer 4.36 (d, J = 4.1 Hz, 2H), minor rotamer 4.28 (d, J =4.2 Hz, 1H), major rotamer 4.06 (q, J = 8.8 Hz, 2H), minor rotamer 3.89(q, = 8.3 Hz, 1H), minor rotamer 3.57 (q, J = 7.1 Hz, 1H), major rotamer3.51 (q, J = 7.2 Hz, 2H), major rotamer 1.29 (t, J = 7.2 Hz, 2H), minorrotamer 1.19 (t, J = 7.1 Hz, 1H). F168 657 ([M + H]⁺) ¹H NMR (500 MHz,¹⁹F NMR CDCl₃) δ 7.86 (d, J = 1.6 Hz, (471 MHz, 1H), CDCl₃) δ 7.76 (dd,J = 8.1, 1.7 Hz, −59.04, 1H), 7.55 (d, J = 8.1 Hz, −69.30 (d, J = 8.6Hz), 1H), 7.44 (s, 2H), −84.57 (dtt, J = 199.2, 7.41 (d, J = 7.0 Hz,12.8, 6.4 Hz), 1H), 6.94 (d, J = 7.7 Hz, −97.82-−98.39 (m), 1H), 5.84(dd, J = 32.5, −112.06 (d, J = 32.8 Hz); 9.6 Hz, 1H), IR (thin film)4.79 (p, J = 7.1 Hz, 1640. 1174, 1H), 4.61 (p, J = 8.9 Hz, 1138, 1118,1H), 732 cm⁻¹ 4.20-4.09 (m, 1H), 2.97-2.80 (m, 2H), 2.52-2.34 (m, 2H),1.49 (d, J = 6.9 Hz, 3H) F169 665 ([M + H]⁺) ¹H NMR (300 MHz, IR (thinfilm) CDCl₃) δ 9.36 (s, 1641 cm⁻¹ 1H), 7.85 (s, 1H), 7.76 (d, J = 8.3Hz, 1H), 7.54 (d, J = 8.1 Hz, 1H), 7.44 (s, 2H), 6.70 (d, J = 7.4 Hz,1H), 5.83 (dd, J = 32.5, 9.6 Hz, 1H), 5.34 (m, 1H), 4.60 (p, J = 8.8 Hz,1H), 4.30 (dt, J = 17.0, 8.4 Hz, 1H), 4.15 (dq, J = 16.8, 8.6 Hz, 1H),1.52 (d, J = 6.9 Hz, 3H) F170 643 ([M + H]⁺) ¹H NMR (300 MHz, IR (thinfilm) CDCl₃) δ 7.85 (d, J = 1.7 Hz, 1648 cm⁻¹ 1H), 7.76 (m, 1H), 7.56(d, J = 8.1 Hz, 1H), 7.39 (m, 5H), 6.99 (m, 2H), 6.91 (m, 2H), 6.47 (d,J = 7.5 Hz, 1H), 5.83 (dd, J = 32.8, 9.8 Hz, 1H), 5.06 (s, 2H), 4.78 (p,J = 7.0 Hz, 1H), 4.59 (p, J = 9.0 Hz, 1H), 3.90 (dq, J = 11.7, 9.0, 6.5Hz, 2H), 1.52 (d, J = 7.0 Hz, 3H) F171 661 ([M + H]⁺) ¹H NMR (300 MHz,IR (thin film) CDCl₃) δ 7.86 (s, 1661 cm⁻¹ 1H), 7.79 (d, J = 8.1 Hz,1H), 7.65 (d, J = 8.1 Hz, 1H), 7.44 (s, 2H), 6.41 (d, J = 5.3 Hz, 1H),5.83 (dd, J = 32.5, 9.6 Hz, 1H), 4.59 (m, 2H), 4.08 (dq, J = 14.9, 9.0Hz, 1H), 3.83 (m, 1H), 3.59 (m, 2H), 2.95 (m, 1H), 2.08 (m, 1H) F172HRMS-ESI (m/z) ¹H NMR (500 MHz, IR (thin film) [M + H]⁺ calcd forDMSO-d₆) δ 8.82 (dd, 3261, 3061, C₂₃H₁₈Cl₃F₇N₂O₂, J = 7.8, 1.5 Hz, 1H),1637, 1552 cm⁻¹ 593.0395; 8.13-8.09 (m, 1H), found, 593.0402 8.05 (s,2H), 8.03 (dd, J = 8.1, 1.7 Hz, 1H), 7.60 (d, J = 8.1 Hz, 1H), 6.79 (dd,J = 35.8, 10.1 Hz, 1H), 5.25 (p, J = 9.4 Hz, 1H), 4.91 (p, J = 7.0 Hz,1H), 3.08 (s, 3H), 2.86 (s, 3H), 1.25 (d, J = 6.9 Hz, 3H) F173 HRMS-ESI(m/z) ¹H NMR (500 MHz, IR (thin film) [M + H]⁺ calcd for DMSO-d₆) δ 8.73(dd, 1652, 1552 cm⁻¹ C₂₂H₁₆Cl₃F₇N₂O₂, J = 7.6, 1.3 Hz, 1H), 579.0238;8.10 (d, J = 1.6 Hz, found, 579.0241 1H), 8.04 (d, J = 10.4 Hz, 3H),7.88 (q, J = 4.7 Hz, 1H), 7.70 (d, J = 8.1 Hz, 1H), 6.79 (dd, J = 35.7,10.1 Hz, 1H), 5.25 (p, J = 9.4 Hz, 1H), 4.42 (p, J = 7.2 Hz, 1H), 2.63(d, J = 4.6 Hz, 3H), 1.27 (d, J = 7.1 Hz, 3H) F174 659 ([M + H]⁺) ¹H NMR(400 MHz, ¹⁹F NMR CDCl₃) δ 7.83 (d, J = 1.8 Hz, (471 MHz, 1H), 7.74 (dt,CDCl₃) δ J = 8.4, 2.5 Hz, 1H), −59.09, 7.53 (dd, J = 8.1, 4.4 Hz,−72.58, 1H), 7.42 (d, J = 3.0 Hz, −103.79-−105.98 (m), 2H), 7.20 (t,−115.07 J = 6.5 Hz, 1H), 6.64 (dd, J = 7.7, 4.9 Hz, 1H), 5.90 (ddd, J =33.9, 9.7, 2.6 Hz, 1H), 4.95-4.78 (m, 1H), 4.31 (td, J = 14.6, 9.8 Hz,1H), 3.88 (tt, J = 9.1, 7.4 Hz, 2H), 1.95-1.78 (m, 2H), 1.51 (dd, J =7.0, 1.4 Hz, 3H), 1.07 (t, J = 7.4 Hz, 3H) F175 643 ([M + H]⁺) ¹H NMR(400 MHz, ¹⁹F NMR CDCl₃) δ 7.87 (s, (376 MHz, 1H), 7.78 (d, J = 8.1 Hz,CDCl₃) δ 1H), 7.56 (d, J = 8.1 Hz, −59.18, 1H), 7.50 (s, −69.26 (d, J =2.1 Hz), 1H), 7.47 (s, 1H), −72.60, 7.42 (s, 1H), 7.06 (t, −88.20 (d, J= 7.0 Hz), J = 6.4 Hz, 1H), −112.61; 6.59 (d, J = 7.6 Hz, 1H), IR (thinfilm) 5.88 (dd, J = 32.6, 3288, 1729, 9.7 Hz, 1H), 4.82 (p, 1647 cm⁻¹ J= 7.0 Hz, 1H), 4.69 (p, J = 8.9 Hz, 1H), 3.98-3.83 (m, 2H), 1.93 (t, J =18.2 Hz, 3H), 1.52 (d, J = 7.0 Hz, 3H) F176 661 ([M + H]⁺) ¹H NMR (400MHz, ¹⁹F NMR CDCl₃) δ 7.87 (s, (376 MHz, 1H), 7.79 (d, J = 8.0 Hz,CDCl₃) δ 1H), 7.58 (d, J = 8.0 Hz, −59.10, 1H), 7.39 (s, −65.69, 1H),7.32 (s, 1H), −69.28 (d, J = 2.2 Hz), 7.22 (s, 1H), 6.63 (s, −72.58,1H), 6.31 (d, J = 8.4 Hz, −112.78; 1H), 5.87 (dd, J = 32.5, IR (thinfilm) 9.8 Hz, 1H), 3272, 1640, 4.77-4.59 (m, 2H), 1539 cm⁻¹ 4.04-3.87(m, 2H), 3.38 (q, J = 10.4 Hz, 2H), 1.51 (d, J = 7.0 Hz, 3H) F177 643([M + H]⁺) ¹H NMR (500 MHz, ¹⁹F NMR CDCl₃) δ 7.87 (s, (471 MHz, 1H),7.79 (d, J = 8.1 Hz, CDCl₃) δ 1H), 7.63 (d, J = 8.1 Hz, −59.03, 1H),7.40 (s, −70.32, 2H), 6.51 (d, J = 4.5 Hz, −113.08, 1H), 6.01 (td, J =55.7, −118.37-−123.39 (m) 2.9 Hz, 1H), 5.84 (dd, J = 33.9, 9.5 Hz, 1H),5.02 (t, J = 8.4 Hz, 1H), 4.97-4.91 (m, 1H), 4.36 (tdd, J = 15.8, 9.4,2.8 Hz, 1H), 4.28-4.07 (m, 3H) F178 675 ([M + H]⁺) ¹H NMR (300 MHz, IR(thin film) CDCl₃) δ 7.89 (s, 3268, 1728, 1H), 7.81 (d, J = 8.0 Hz,1659, 1538 cm⁻¹ 1H), 7.64 (d, J = 8.3 Hz, 1H), 7.40 (s, 1H), 7.33 (s,1H), 7.22 (s, 1H), 6.39 (s, 1H), 5.88 (dd, J = 32.6, 9.7 Hz, 1H), 5.04(t, J = 8.2 Hz, 1H), 5.00-4.87 (m, 1H), 4.74-4.56 (m, 1H), 4.33-4.05 (m,3H), 3.39 (q, J = 10.6 Hz, 2H) F180 661 ([M + H]⁺) ¹H NMR (400 MHz, ¹⁹FNMR CDCl₃) δ 7.88 (s, (376 MHz, 1H), 7.81 (d, J = 8.2 Hz, CDCl₃) δ 1H),7.74 (d, J = 8.2 Hz, −59.03, 1H), 7.65 (d, −62.80, J = 8.0 Hz, 1H),−69.07 (d, J = 2.2 Hz), 7.57 (s, 1H), 7.43 (d, J = 7.7 Hz, −70.29, 1H),6.37 (s, −112.11; 1H), 5.89 (dd, J = 32.6, IR (thin film) 9.6 Hz, 1H),3268, 1669, 5.04 (t, J = 8.4 Hz, 1533 cm⁻¹ 1H), 4.99-4.90 (m, 1H), 4.71(p, J = 9.0 Hz, 1H), 4.31-4.07 (m, 3H) F181 663 ([M + H]⁺) ¹H NMR (400MHz, ¹⁹F NMR CDCl₃) δ 7.87 (d, J = 1.6 Hz, (376 MHz, 1H), CDCl₃) δ7.83-7.76 (m, 1H), −57.94, 7.58 (d, J = 8.1 Hz, 1H), −59.15, 7.35 (s,1H), 7.27 (s, −69.27 (d, J = 2.5 Hz), 1H), 7.17 (s, 1H), −72.59, 6.86(t, J = 6.3 Hz, −112.15 (d, J = 2.6 Hz); 1H), 6.47 (d, J = 7.5 Hz, IR(thin film) 1H), 5.85 (dd, J = 32.5, 3284, 1652, 9.7 Hz, 1H), 1540 cm⁻¹4.78 (p, J = 7.1 Hz, 1H), 4.66 (p, J = 8.9 Hz, 1H), 3.93 (qd, J = 8.9,6.4 Hz, 2H), 1.52 (d, J = 7.0 Hz, 3H) F182 663 ([M + H]⁺) ¹H NMR (400MHz, ¹⁹F NMR CDCl₃) δ 7.87 (d, J = 1.5 Hz, (376 MHz, 1H), CDCl₃) δ 7.78(dd, J = 8.3, 1.7 Hz, −57.82, 1H), 7.57 (d, J = 8.1 Hz, −59.15, 1H),7.53 (d, J = 1.6 Hz, −69.39 (d, J = 2.2 Hz), 1H), −72.59, 7.39-7.31 (m,2H), −112.62 (d, J = 2.3 Hz); 6.86 (s, 1H), 6.46 (d, J = 7.5 Hz, IR(thin film) 1H), 3285, 1648, 5.87 (dd, J = 32.6, 9.7 Hz, 1545, 1497 cm⁻¹1H), 4.78 (p, J = 7.1 Hz, 1H), 4.67 (p, J = 8.9 Hz, 1H), 3.92 (qd, J =9.0, 6.4 Hz, 2H), 1.52 (d, J = 7.0 Hz, 3H) F183 663 ([M + H]⁺) ¹H NMR(400 MHz, ¹⁹F NMR CDCl₃) δ 7.86 (d, J = 1.4 Hz, (376 MHz, 1H), 7.78 (d,CDCl₃) δ J = 8.2 Hz, 1H), −57.85, 7.58 (d, J = 8.1 Hz, 1H), −59.15, 7.52(d, J = 8.4 Hz, −69.52 (d, J = 2.4 Hz), 1H), 7.36 (s, 1H), −72.59, 7.31(dd, J = 8.3, 2.1 Hz, −112.31; 1H), 6.78 (t, J = 6.4 Hz, IR (thin film)1H), 6.42 (d, 3284, 1646, J = 7.5 Hz, 1H), 1540, 1491 cm⁻¹ 5.86 (dd, J =32.6, 9.6 Hz, 1H), 4.76 (p, J = 7.2 Hz, 1H), 4.66 (q, J = 8.9 Hz, 1H),4.00-3.87 (m, 2H), 1.51 (d, J = 7.0 Hz, 4H) F184 629 ([M − H]⁻) ¹H NMR(400 MHz, ¹⁹F NMR CDCl₃) δ 7.85 (s, (376 MHz, 1H), 7.75 (d, J = 8.3 Hz,CDCl₃) δ 1H), 7.52 (d, J = 8.0 Hz, −59.23 (d, J = 4.8 Hz), 1H), 7.48 (s,−66.70-−70.14 (m), 2H), 7.38 (q, J = 6.7, −72.62, 5.8 Hz, 1H),−108.70-−115.95 (m) 7.14 (dd, J = 17.4, 11.0 Hz, 2H), 6.80 (d, J = 7.8Hz, 1H), 6.02-5.83 (m, 1H), 5.74 (d, J = 17.4 Hz, 2H), 5.45 (d, J = 11.0Hz, 2H), 4.89 (p, J = 7.1 Hz, 1H), 4.67 (p, J = 9.0 Hz, 1H), 3.99-3.74(m, 2H), 1.51 (d, J = 6.9 Hz, 3H) F185 692 ([M − H]⁻) ¹H NMR (400 MHz,¹⁹F NMR CDCl₃) δ (376 MHz, 7.89-7.82 (m, 2H), 7.76 (dd, J = 8.0, CDCl₃)δ 1.7 Hz, 1H), −59.24, 7.60 (d, J = 2.1 Hz, −69.31 (d, J = 2.2 Hz), 1H),7.56 (d, J = 8.1 Hz, −72.97 (d, J = 271.5 Hz), 1H), 7.48 (d, J = 2.1 Hz,−112.04 (d, J = 14.3 Hz) 1H), 6.77 (d, J = 7.6 Hz, 1H), 5.84 (dd, J =32.5, 9.6 Hz, 1H), 4.86 (p, J = 7.0 Hz, 1H), 4.60 (p, J = 8.8 Hz, 1H),3.88 (dddd, J = 15.6, 9.0, 7.6, 1.8 Hz, 2H), 1.52 (d, J = 7.0 Hz, 3H)F186 639 ([M − H]⁻) ¹H NMR (400 MHz, ¹⁹F NMR CDCl₃) δ 7.86 (d, J = 1.6Hz, (376 MHz, 1H), CDCl₃) δ 7.77 (dd, J = 8.0, 1.7 Hz, −56.83-−60.72(m), 1H), 7.55 (dd, J = 8.1, −67.67-−71.03 (m), 2.8 Hz, 1H), −72.94 (d,J = 254.5 Hz), 7.50-7.37 (m, 2H), −113.05 (d, J = 249.6 Hz) 7.22-7.03(m, 2H), 6.65 (dd, J = 7.8, 4.7 Hz, 1H), 5.93-5.81 (m, 1H), 5.76 (ddd, J= 17.5, 13.4, 0.9 Hz, 1H), 5.56-5.37 (m, 1H), 4.84 (p, J = 7.1 Hz, 1H),4.66 (dt, J = 12.8, 9.1 Hz, 1H), 4.04-3.69 (m, 2H), 1.51 (d, J = 6.9 Hz,3H) F187 653 ([M − H]⁻) ¹H NMR (400 MHz, ¹⁹F NMR CDCl₃) δ 7.84 (d, J =1.6 Hz, (376 MHz, 1H), CDCl₃) δ 7.74 (dd, J = 8.0, 1.7 Hz, −51.53-−61.54(m), 1H), 7.61-7.48 (m, −67.07-−70.14 (m), 2H), 7.43 (d, J = 2.2 Hz,−72.64, 1H), 7.14 (d, J = 2.2 Hz, −113.01 1H), 7.07-6.95 (m, 1H), 5.86(dd, J = 32.7, 9.7 Hz, 1H), 5.27 (p, J = 1.5 Hz, 1H), 5.04-4.97 (m, 1H),4.92 (p, J = 7.1 Hz, 1H), 4.62 (p, J = 9.0 Hz, 1H), 3.93-3.72 (m, 2H),2.10 (t, J = 1.2 Hz, 3H), 1.51 (d, J = 6.9 Hz, 3H) F188 653 ([M − H]⁻)¹H NMR (400 MHz, ¹⁹F NMR CDCl₃) δ 7.84 (s, (376 MHz, 1H), 7.75 (dd, J =8.1, CDCl₃) δ 1.8 Hz, 1H), −57.06-−61.17 (m), 7.53 (dd, J = 8.1, 3.6 Hz,−67.37-−70.81 (m), 1H), −72.61, 7.45-7.30 (m, 3H), −110.79-−115.95 (m)6.92-5.75 (m, 4H), 4.88 (p, J = 7.1 Hz, 1H), 4.62 (ddq, J = 13.1, 9.0,4.3 Hz, 1H), 3.86 (qdd, J = 8.9, 6.3, 2.5 Hz, 2H), 2.01-1.73 (m, 3H),1.51 (d, J = 6.9 Hz, 3H) F189 638 ([M + H]⁺) ¹H NMR (400 MHz, ¹⁹F NMRCDCl₃) δ 7.87 (d, J = 1.6 Hz, (376 MHz, 1H), CDCl₃) δ 7.83-7.71 (m, 1H),−59.14, 7.57 (d, J = 8.1 Hz, 1H), −67.97-−70.44 (m), 7.54-7.40 (m, 2H),−72.59, 6.87 (t, J = 6.5 Hz, −106.38-−115.05 (m) 1H), 6.46 (d, J = 7.5Hz, 1H), 5.85 (ddd, J = 32.6, 9.7, 5.1 Hz, 1H), 4.78 (p, J = 7.1 Hz,1H), 4.61 (p, J = 9.1 Hz, 1H), 4.03-3.84 (m, 2H), 3.52-3.39 (m, 1H),1.52 (d, J = 7.0 Hz, 3H) F190 649 ([M − H]⁻) ¹H NMR (400 MHz, ¹⁹F NMRCDCl₃) δ (376 MHz, 7.91-7.82 (m, 1H), 7.77 (dd, J = 8.2, CDCl₃) δ 1.7Hz, 1H), −59.15, 7.61-7.50 (m, 1H), −66.85-−70.44 (m), 7.45-7.34 (m,2H), −72.59, 6.95 (t, J = 6.4 Hz, −108.10-−114.23 (m) 1H), 6.51 (d, J =7.6 Hz, 1H), 5.83 (dd, J = 32.6, 9.8 Hz, 1H), 4.79 (p, J = 7.1 Hz, 1H),4.58 (p, J = 8.9 Hz, 1H), 4.02-3.83 (m, 2H), 2.14 (s, 3H), 1.52 (d, J =7.0 Hz, 3H) F191 691 ([M − H]⁻) ¹H NMR (400 MHz, ¹⁹F NMR CDCl₃) δ 7.87(s, (376 MHz, 1H), 7.79 (d, J = 8.1 Hz, CDCl₃) δ 1H), −56.24-−60.94 (m),7.63-7.54 (m, 1H), −67.15-−69.91 (m), 7.41-7.33 (m, 2H), 6.68 (s,−73.26, 1H), 6.35 (d, J = 7.5 Hz, −112.60 (d, J = 21.4 Hz) 1H), 5.84(dd, J = 32.6, 9.7 Hz, 1H), 4.73 (p, J = 7.2 Hz, 1H), 4.58 (p, J = 8.7Hz, 1H), 4.03-3.80 (m, 2H), 1.51 (d, J = 7.0 Hz, 3H), 1.35 (s, 9H) F192636 ([M − H]⁻) ¹H NMR (400 MHz, ¹⁹F NMR CDCl₃) δ 7.87 (d, J = 1.7 Hz,(376 MHz, 1H), CDCl₃) δ 7.78 (dd, J = 8.1, 1.8 Hz, −59.23, 1H), 7.75 (s,1H), −67.15-−70.73 (m), 7.65 (d, J = 2.1 Hz, −72.59, 1H), 7.58 (d, J =8.1 Hz, −107.51-−115.88 (m) 1H), 7.15 (t, J = 6.4 Hz, 1H), 6.70 (d, J =7.7 Hz, 1H), 5.96-5.74 (m, 1H), 4.84 (p, J = 7.1 Hz, 1H), 4.68 (p, J =8.7 Hz, 1H), 3.97-3.81 (m, 2H), 1.52 (d, J = 7.0 Hz, 3H) F193 675 ([M −H]⁻) ¹H NMR (400 MHz, ¹⁹F NMR CDCl₃) δ 7.85 (dd, J = 9.3, (376 MHz, 1.8Hz, 1H), CDCl₃) δ 7.80-7.71 (m, 1H), −57.66-−60.42 (m), 7.61 (d, J = 2.2Hz, −69.34 (d, J = 2.3 Hz), 1H), 7.56 (d, J = 8.1 Hz, −72.58, 2H), 7.26(s, 1H), −87.48, 6.75 (d, J = 7.7 Hz, −106.98-−114.23 (m) 1H), 5.86 (dd,J = 32.6, 9.6 Hz, 1H), 4.86 (p, J = 7.0 Hz, 1H), 4.67 (p, J = 8.9 Hz,1H), 4.01-3.81 (m, 2H), 2.18-1.93 (m, 3H), 1.52 (dd, J = 7.0, 4.5 Hz,3H) F194 643 ([M − H]⁻) ¹H NMR (400 MHz, ¹⁹F NMR CDCl₃) δ (376 MHz,7.90-7.82 (m, 1H), 7.75 (dd, J = 8.1, CDCl₃) δ 1.7 Hz, 1H),−58.60-−60.17 (m), 7.54 (d, J = 8.1 Hz, −68.68-−69.62 (m), 1H), 7.52 (s,1H), −72.63 (d, J = 2.5 Hz), 7.44 (d, J = 2.1 Hz, −73.34, 1H), 7.34 (t,J = 6.5 Hz, −107.80-−115.05 (m) 1H), 6.82 (d, J = 7.7 Hz, 1H), 5.99-5.77(m, 1H), 5.58 (s, 1H), 5.46 (s, 1H), 4.86 (p, J = 7.1 Hz, 1H), 4.66 (h,J = 9.0 Hz, 1H), 3.94-3.77 (m, 2H), 1.51 (d, J = 7.0 Hz, 3H) F195 661([M − H]⁻) ¹H NMR (400 MHz, ¹⁹F NMR CDCl₃) δ 7.86 (s, (376 MHz, 1H),7.78 (dd, J = 8.1, CDCl₃) δ 1.7 Hz, 1H), −59.2, 7.63 (d, J = 12.0 Hz,−69.36, 2H), 7.57 (d, J = 8.1 Hz, −72.66, 1H), −110.57, 7.09-7.02 (m,1H), 6.88 (t, J = 54.6 Hz, −115.6 1H), 6.62 (d, J = 7.6 Hz, 1H), 5.87(dd, J = 32.5, 9.6 Hz, 1H), 4.82 (p, J = 7.1 Hz, 1H), 4.70 (p, J = 8.9Hz, 1H), 4.02-3.73 (m, 2H), 1.51 (d, J = 7.0 Hz, 3H) F196 651 ([M − H]⁻)¹H NMR (400 MHz, ¹⁹F NMR CDCl₃) δ 7.87 (d, J = 1.6 Hz, (376 MHz, 1H),CDCl₃) δ 7.78 (dd, J = 8.1, 1.7 Hz, −59.07 (d, J = 3.0 Hz), 1H), 7.62(d, J = 8.1 Hz, −67.15-−69.91 (m), 1H), 7.47 (d, J = 2.0 Hz, −70.35 (d,J = 4.9 Hz), 1H), 7.44 (d, −109.22-−116.70 (m) J = 2.1 Hz, 1H), 7.09(dd, J = 17.5, 11.0 Hz, 1H), 6.64 (d, J = 4.6 Hz, 1H), 5.96-5.82 (m,1H), 5.78 (d, J = 17.4 Hz, 1H), 5.56-5.46 (m, 1H), 5.09-4.86 (m, 2H),4.65 (p, J = 9.0 Hz, 1H), 4.33-4.02 (m, 3H) F197 705 ([M − H]⁻) ¹H NMR(400 MHz, ¹⁹F NMR CDCl₃) δ 7.86 (d, J = 1.6 Hz, (376 MHz, 1H), CDCl₃) δ7.77 (dd, J = 8.0, 1.7 Hz, −59.12 (d, J = 3.4 Hz), 1H), 7.66-7.57 (m,−69.32 (d, J = 2.1 Hz), 2H), 7.49 (d, J = 2.0 Hz, −70.40 (d, J = 6.8Hz), 1H), 6.85 (d, J = 4.1 Hz, −109.22-−114.23 (m) 1H), 5.86 (dd, J =32.5, 9.6 Hz, 1H), 5.02-4.88 (m, 2H), 4.61 (p, J = 8.9 Hz, 1H),4.28-4.01 (m, 3H) F198 672 ([M − H]⁻) ¹H NMR (400 MHz, ¹⁹F NMR CDCl₃) δ7.79 (d, J = 1.6 Hz, (376 MHz, 1H), 7.62 (d, CDCl₃) δ J = 8.1 Hz, 1H),−69.33 (d, J = 2.3 Hz), 7.56 (dd, J = 8.2, 1.6 Hz, −70.28, 1H), 7.43 (s,2H), −110.63-−114.49 (m) 6.79 (dd, J = 11.5, 4.4 Hz, 1H), 5.78 (dd, J =32.6, 9.6 Hz, 1H), 5.07-4.91 (m, 2H), 4.58 (p, J = 8.9 Hz, 1H),4.31-4.05 (m, 3H) F199 674 ([M − H]⁻) ¹H NMR (400 MHz, ¹⁹F NMR CDCl₃) δ7.88 (d, J = 2.0 Hz, (376 MHz, 1H), CDCl₃) δ 7.78 (ddd, J = 10.2, 7.0,−59.07 (d, J = 1.4 Hz), 2.0 Hz, 2H), −69.35 (d, J = 2.3 Hz), 7.69-7.57(m, 2H), −70.34, 6.95 (t, J = 54.6 Hz, 1H), −111.83 (d, J = 46.3 Hz),6.59 (dd, J = 13.3, −115.77 4.4 Hz, 1H), 5.98-5.81 (m, 1H), 5.05-4.84(m, 2H), 4.80-4.65 (m, 1H), 4.34-4.02 (m, 3H) F200 592 ([M − H]⁻) ¹H NMR(400 MHz, ¹⁹F NMR CDCl₃) δ 7.71 (d, J = 1.6 Hz, (376 MHz, 1H), 7.53 (d,CDCl₃) δ J = 8.1 Hz, 1H), −69.37, 7.48 (dd, J = 10.7, 2.1 Hz, −72.46,1H), 7.44 (s, 2H), −111.55 7.24 (d, J = 16.1 Hz, 1H), 7.12-6.97 (m, 1H),6.88 (t, J = 5.3 Hz, 1H), 5.91-5.65 (m, 2H), 5.51-5.40 (m, 1H), 4.62(dp, J = 13.5, 9.0 Hz, 1H), 4.23 (d, J = 5.3 Hz, 2H), 3.93 (qd, J = 9.0,6.3 Hz, 2H) F201 604 ([M − H]⁻) ¹H NMR (400 MHz, ¹⁹F NMR CDCl₃) δ 7.68(s, (376 MHz, 1H), 7.46 (d, J = 1.6 Hz, CDCl₃) δ 3H), 7.44 (s, 2H),−69.37, 6.97 (dd, J = 17.4, −72.51 11.0 Hz, 1H), −73.27, 6.76 (d, J =7.6 Hz, 1H), −111.56 5.80 (d, J = 8.8 Hz, 1H), 5.76-5.65 (m, 1H),5.51-5.35 (m, 1H), 4.83 (p, J = 7.1 Hz, 1H), 4.60 (p, J = 8.9 Hz, 1H),3.86 (dqd, J = 27.8, 9.1, 6.4 Hz, 2H), 1.57-1.44 (m, 3H) F202 662 ([M −H]⁻) ¹H NMR (400 MHz, ¹⁹F NMR CDCl₃) δ 7.82 (d, J = 1.7 Hz, (376 MHz,1H), CDCl₃) δ 7.72 (ddd, J = 9.7, 6.2, −59.46, 3.9 Hz, 2H), 7.54 (s,−62.62, 1H), 7.51 (d, J = 8.1 Hz, −69.52, 1H), 7.44 (dd, J = 8.9,−72.74, 2.0 Hz, 1H), −109.56, 7.29-7.24 (m, 1H), −111.73 5.86 (dd, J =32.5, 9.5 Hz, 1H), 4.94 (p, J = 7.1 Hz, 1H), 4.72 (p, J = 8.8 Hz, 1H),3.87-3.67 (m, 2H), 1.50 (d, J = 6.9 Hz, 3H) F203 650 ([M − H]⁻) ¹H NMR(400 MHz, ¹⁹F NMR CDCl₃) δ (376 MHz, 7.90-7.81 (m, 1H), 7.77 (dd, J =8.1, CDCl₃) δ 1.7 Hz, 1H), −59.53, 7.59 (d, J = 8.1 Hz, −62.59, 1H),7.54 (s, 1H), −69.48 (d, J = 2.3 Hz), 7.50 (t, J = 6.5 Hz, −72.63, 1H),7.44 (dd, J = 8.9, −109.50 2.0 Hz, 1H), 7.24 (t, J = 5.2 Hz, 1H), 5.88(dd, J = 32.5, 9.5 Hz, 1H), 4.72 (p, J = 8.8 Hz, 1H), 4.25 (d, J = 5.1Hz, 2H), 3.86 (qd, J = 9.0, 6.5 Hz, 2H) F204 618 ([M − H]⁻) ¹H NMR (400MHz, ¹⁹F NMR CDCl₃) δ 7.70 (d, J = 1.6 Hz, (376 MHz, 1H), 7.56 (d,CDCl₃) δ J = 8.2 Hz, 1H), −69.35, 7.49 (dd, J = 8.3, 1.8 Hz, −70.30,1H), 7.44 (s, 2H), −75.43, 7.11-6.99 (m, 1H), −1114.59 6.57 (d, J = 3.9Hz, 1H), 5.84-5.78 (m, 1H), 5.78-5.70 (m, 1H), 5.51-5.42 (m, 1H),5.06-4.80 (m, 1H), 4.60 (p, J = 8.9 Hz, 1H), 4.30-4.01 (m, 4H) F205 647([M + H]⁺) ¹H NMR (400 MHz, ¹⁹F NMR CDCl₃) δ 7.87 (s, (376 MHz, 1H),7.79 (d, J = 8.1 Hz, CDCl₃) δ 1H), 7.74 (d, J = 8.2 Hz, −59.12, 1H),7.58 (d, −62.80, J = 11.0 Hz, 2H), −69.10 (d, J = 2.3 Hz), 7.42 (d, J =8.2 Hz, −72.58, 1H), 6.67 (s, 1H), −112.08; 6.36 (d, J = 7.4 Hz, IR(thin film) 1H), 5.88 (dd, J = 32.6, 3288, 1652, 9.6 Hz, 1H), 1540 cm⁻¹4.89-4.58 (m, 2H), 3.93 (pd, J = 8.9, 6.5 Hz, 2H), 1.51 (d, J = 7.0 Hz,3H) F206 633 ([M + H]⁺) ¹H NMR (400 MHz, ¹⁹F NMR CDCl₃) δ 7.89 (d, J =1.7 Hz, (376 MHz, 1H), CDCl₃) δ 7.84-7.77 (m, 1H), −59.27, 7.74 (d, J =8.2 Hz, 1H), −62.80, 7.62 (d, J = 8.1 Hz, −69.09 (d, J = 2.3 Hz), 1H),7.57 (s, 1H), −72.54, 7.43 (d, J = 8.1 Hz, −112.13 (d, J = 2.9 Hz); 1H),6.64 (dd, J = 10.0, IR (thin film) 5.3 Hz, 2H), 3299, 1655, 5.89 (dd, J= 32.6, 1538 cm⁻¹ 9.6 Hz, 1H), 4.71 (p, J = 8.9 Hz, 1H), 4.22 (d, J =5.3 Hz, 2H), 3.95 (qd, J = 8.9, 6.5 Hz, 2H) F207 675 ([M − H]⁻) ¹H NMR(400 MHz, ¹⁹F NMR CDCl₃) δ (376 MHz, 7.95-7.83 (m, 1H), 7.78 (d, J = 8.0Hz, CDCl₃) δ 1H), 7.57 (d, −59.13, J = 8.1 Hz, 1H), −69.19 (d, J = 2.4Hz), 7.10 (s, 1H), 6.94 (t, J = 2.0 Hz, −72.58, 1H), 6.91 (s, −73.82,1H), 6.84 (t, J = 6.4 Hz, −113.00 (d, J = 54.0 Hz); 1H), 6.44 (d, J =7.5 Hz, IR (thin film) 1H), 3290, 2963, 5.85 (dd, J = 32.6, 9.7 Hz,1652, 1538 cm⁻¹ 1H), 4.77 (p, J = 7.0 Hz, 1H), 4.62 (p, J = 9.2 Hz, 1H),4.36 (q, J = 7.9 Hz, 2H), 4.05-3.81 (m, 2H), 1.51 (d, J = 7.0 Hz, 3H)F208 691 ([M − H]⁻) ¹H NMR (400 MHz, ¹⁹F NMR CDCl₃) δ 7.87 (s, (376 MHz,1H), 7.79 (d, J = 8.1 Hz, CDCl₃) δ 1H), 7.76 (s, 1H), −58.18-−59.72 (m),7.73 (d, J = 8.2 Hz, −62.84, 1H), 7.58 (d, J = 8.1 Hz, −68.86 (d, J =2.3 Hz), 1H), 7.47 (d, J = 8.2 Hz, −72.58, 1H), 6.70 (s, −112.07; 1H),6.37 (s, 1H), IR (thin film) 5.88 (dd, J = 32.6, 3289, 3087, 9.6 Hz,1H), 4.70 (dt, 1651, 1540 cm⁻¹ J = 18.1, 8.9 Hz, 2H), 3.94 (p, J = 8.1,7.6 Hz, 2H), 1.52 (d, J = 7.0 Hz, 3H) F209 679 ([M + H]⁺) ¹H NMR (400MHz, ¹⁹F NMR CDCl₃) δ (376 MHz, 7.91-7.87 (m, 1H), 7.80 (d, J = 1.8 Hz,CDCl₃) δ 1H), −59.36, 7.79-7.75 (m, 1H), −62.85, 7.73 (d, J = 8.2 Hz,1H), −69.09 (d, J = 2.3 Hz), 7.61 (d, J = 8.1 Hz, −72.56, 1H), 7.48 (d,J = 8.4 Hz, −112.16 (d, J = 2.7 Hz); 1H), 7.10 (s, 1H), IR (thin film)6.88 (s, 1H), 3302, 3084, 5.89 (dd, J = 32.6, 9.6 Hz, 1655, 1537 cm⁻¹1H), 4.71 (p, J = 8.9 Hz, 1H), 4.41-4.14 (m, 2H), 3.92 (qd, J = 9.0, 6.6Hz, 2H) F211 617 ([M + H]⁺) ¹H NMR (400 MHz, ¹⁹F NMR CDCl₃) δ 7.86 (d, J= 1.7 Hz, (376 MHz, 1H), CDCl₃) δ 7.77 (dd, J = 8.1, 1.7 Hz, −59.39,1H), 7.66-7.57 (m, −61.54 (d, J = 12.4 Hz), 3H), 7.45 (t, J = 6.5 Hz,−69.69 (d, J = 2.4 Hz), 1H), −72.51, 7.31-7.21 (m, 1H), 7.04 (t, J = 5.1Hz, −112.48, 1H), −113.88 (q, J = 12.7 Hz); 5.90 (dd, J = 32.6, 9.6 Hz,IR (thin film) 1H), 4.72 (p, J = 8.9 Hz, 3294, 1656, 1H), 4.26 (d, J =5.1 Hz, 1539 cm⁻¹ 2H), 3.92 (qd, J = 9.0, 6.4 Hz, 2H) F212 EIMS 658 ¹HNMR (400 MHz, ¹⁹F NMR CDCl₃) δ 7.83 (d, J = 1.6 Hz, (376 MHz, 1H),CDCl₃) δ 7.73 (dd, J = 8.1, 1.7 Hz, −59.30, 1H), 7.58 (t, J = 6.5 Hz,−69.24, 1H), 7.51 (d, J = 8.1 Hz, −72.64, 1H), −113.27 (d, J = 29.5 Hz)7.40-7.37 (m, 1H), 7.30 (d, J = 1.5 Hz, 1H), 7.29 (d, J = 1.9 Hz, 1H),7.02 (d, J = 7.8 Hz, 1H), 5.86 (dd, J = 32.7, 9.8 Hz, 1H), 4.91 (p, J =7.1 Hz, 1H), 4.74-4.51 (m, 1H), 3.83 (dtd, J = 12.3, 8.8, 6.3 Hz, 2H),1.50 (d, J = 6.9 Hz, 3H), 1.31 (s, 9H) F213 EIMS 628 ¹H NMR (300 MHz, IR(thin film) CDCl₃) δ 7.85 (t, J = 1.9 Hz, 3266, 2922, 1H), 1653, 1114cm⁻¹ 7.76 (dd, J = 8.2, 1.8 Hz, 1H), 7.64-7.50 (m, 3H), 7.44 (s, 1H),7.35 (s, 1H), 6.97-6.41 (m, 2H), 5.88 (ddd, J = 32.7, 9.7, 7.4 Hz, 1H),4.85 (p, J = 7.0 Hz, 1H), 4.70 (p, J = 8.9 Hz, 1H), 3.89-3.72 (m, 2H),1.51 (d, J = 7.0 Hz, 3H) F214 661 ([M + H]⁺) ¹H NMR (400 MHz, ¹⁹F NMRCDCl₃) δ 7.83 (dd, J = 12.3, (376 MHz, 1.8 Hz, 1H), CDCl₃) δ 7.74 (dd, J= 8.1, 1.7 Hz, −59.34 (d, J = 24.1 Hz), 1H), 7.63 (t, J = 6.5 Hz,−68.79, 1H), 7.54 (d, −70.14, J = 8.1 Hz, 1H), −72.59, 7.41-7.37 (m,1H), −129.23 (d, J = 21.5 Hz), 7.22 (ddd, J = 10.2, 6.7, −132.24 (d, J =21.5 Hz) 2.2 Hz, 1H), 7.07 (d, J = 7.7 Hz, 1H), 5.83 (dd, J = 32.6, 9.6Hz, 1H), 4.95-4.81 (m, 1H), 4.71-4.50 (m, 1H), 3.94-3.76 (m, 2H), 1.49(dd, J = 7.0, 4.1 Hz, 3H) F215 565 ([M − H]⁻) ¹H NMR (400 MHz, ¹⁹F NMRCDCl₃) δ 7.88 (d, J = 1.7 Hz, (376 MHz, 1H), CDCl₃) δ 7.79 (dd, J = 8.1,1.8 Hz, −59.31, 1H), 7.62 (d, J = 8.0 Hz, −68.79, 1H), 7.38 (dt, J =4.7, −70.14, 2.0 Hz, 1H), −72.54, 7.26 (s, 2H), 6.89 (t, −129.10 (d, J =21.3 Hz), J = 6.6 Hz, 1H), −132.13 (d, J = 21.4 Hz) 6.76 (t, J = 5.2 Hz,1H), 5.83 (dd, J = 32.5, 9.6 Hz, 1H), 4.61 (p, J = 8.9 Hz, 1H), 4.23 (d,J = 5.3 Hz, 2H), 3.94 (qd, J = 9.0, 6.5 Hz, 2H) F216 EIMS 660 ¹H NMR(400 MHz, ¹⁹F NMR CDCl₃) δ 7.87 (d, J = 2.1 Hz, (376 MHz, 1H), 7.78 (dt,CDCl₃) δ J = 8.0, 2.4 Hz, 1H), −58.10-−59.82 (m), 7.57 (dd, J = 8.1, 2.7Hz, −69.67 (t, J = 3.0 Hz), 1H), 7.51 (t, J = 6.2 Hz, −73.05 (d, J =303.2 Hz), 1H), 7.45-7.36 (m, 1H), −129.41 (d, J = 21.5 Hz,) 7.25-7.12(m, 1H), −135.70 (dd, 7.03 (d, J = 7.6 Hz, 1H), J = 285.5, 5.89 (ddd, J= 32.8, 21.1 Hz) 9.7, 4.8 Hz, 1H), 4.80 (q, J = 7.0 Hz, 1H), 4.61 (dt, J= 14.4, 9.0 Hz, 1H), 3.99-3.78 (m, 2H), 1.50 (dd, J = 6.9, 3.8 Hz, 3H),1.33 (d, J = 3.4 Hz, 9H) F217 645 ([M − H]⁻) ¹H NMR (400 MHz, ¹⁹F NMRCDCl₃) δ 7.85 (dd, J = 11.4, (376 MHz, 1.9 Hz, 1H), CDCl₃) δ 7.79-7.69(m, 1H), −59.44, 7.58 (dd, J = 11.7, −69.09, 7.2 Hz, 2H), 7.39 (dt,−70.51, J = 4.8, 1.8 Hz, 2H), −72.56 (d, J = 1.6 Hz), 7.27-7.17 (m, 1H),−129.27 (d, J = 21.5 Hz), 5.86 (dd, J = 32.6, −132.28 (d, J = 21.4 Hz)9.6 Hz, 1H), 4.69-4.57 (m, 1H), 4.22 (dd, J = 6.8, 5.1 Hz, 3H), 3.89(qd, J = 9.1, 6.5 Hz, 1H)

TABLE 5 Structure and Preparation Method for FC Series Compounds No.Structure Prep.* FC1

13 FC2

13 *prepared according to example number

TABLE 6 Structure and Preparation Method for CC Series Molecules No.Structure Prep* CC1

1 *prepared according to example number

TABLE 7 Analytical Data for Compounds in Table 5 Mp ¹³C NMR; No. (° C.)Mass (m/z) ¹H NMH ¹⁹F NMR; IR FC1 568 ¹H NMR (300 MHz, ¹³C NMR (75 ([M +H]⁺) CDCl₃) δ 7.85 (d, J = MHz, CDCl₃) δ 8.3 Hz, 2H), 7.78- 169.73,167.13, 7.71 (m, 1H), 7.65- 159.34 (d, J_(CF) = 7.57 (m, 3H), 7.43 256.1Hz), (s, 2H), 5.79 (dd, J = 143.29, 134.76, 32.8, 9.6 Hz, 1H), 134.28,133.99, 4.60 (p, J = 8.9 Hz, 133.62, 131.99, 1H), 4.27 (d, J = 5.1128.92, 127.60, Hz, 2H), 3.94 (qd, J = 125.77, 125.27- 9.0, 6.4 Hz, 2H),124.64 (m), 3.52-3.22 (m, 1H) 122.08, 99.74 (d, J_(CF) = 15.0 Hz),47.03, 43.78, 26.35 (d, J = 8.8 Hz) FC2 582 ¹H NMR (300 MHz, ¹³C NMR (75([M + H]⁺) CDCl₃) δ 7.82 (d, J = MHz, CDCl₃) δ 8.2 Hz, 2H), 7.65-173.19, 166.50, 7.56 (m, 2H), 7.43 159.35 (d, J_(CF) = (s, 2H), 7.32(dd, J = 256.0 Hz), 7.5, 2.1 Hz, 1H), 134.76, 134.58, 5.78 (ddd, J =32.8, 134.28, 133.91, 9.6, 0.9 Hz, 1H), 133.54, 131.99, 5.07-4.86 (m,1H), 128.92, 128.14, 4.60 (p, J = 8.9 Hz, 127.57, 127.17 1H), 4.12-3.71(m, 124.84 (d, J_(CF) = 2H), 1.55 (t, J = 6.8 7.1 Hz), f99.58, Hz, 4H)49.35, 34.66, 18.54.

TABLE 8 Structure and Preparation Method for PF Series Molecules No.Structure Prep.* PF1 

13 PF2 

16 PF3 

16 PF4 

13 PF6 

13 PF7 

13 PF8 

13 PF10

16 PF12

16 PF13

16 PF14

16 PF15

16 PF16

16 PF18

16 PF19

16 PF20

16 PF22

16 PF24

16 PF25

16 PF26

16 PF27

16 PF28

16 PF31

16 PF32

16 PF33

16 PF35

16 PF37

16 PF39

16 PF41

16 PF42

16 PF43

16 PF44

16 PF45

16 PF47

16 PF48

16 PF49

16 PF50

16 PF51

16 PF60

16 PF62

16 PF82

51 PF88

52 PF94

52 PF96

13 PF98

13 *prepared according to example number

TABLE 9 Analytical Data for Molecules in Table 8 Mp ¹³C NMR; No. (° C.)Mass (m/z) ¹H NMR ¹⁹F NMR; IR PF1 78-80 629 ([M + H]⁺) ¹H NMR (300 MHz,DMSO-d₆) δ 8.87 (d, J = 6.9 Hz, 1H), 8.69 (t, J = 6.0 Hz, 1H), 8.30 (d,J = 7.5 Hz, 1H), 8.07 (s, 2H), 7.95 (s, 1H), 7.73-7.61 (m, 4H), 6.30(dd, J = 9.9, 33.9 Hz, 1H), 5.35- 5.29 (m, 1H), 4.60- 4.56 (m, 1H),4.11- 3.91 (m, 2H), 1.36 (d, J = 6.9 Hz, 3H) PF2 715 ([M + H]⁺) ¹H NMR(300 MHz, IR (thin film) DMSO-d₆) δ 8.97 (d, J = 3429, 2998, 7.2 Hz,1H), 8.10 (s, 1659, 1031 2H), 8.04 (d, J = 7.8 cm⁻¹ Hz, 1H), 7.86 (d, J= 8.1 Hz, 1H), 7.61- 7.56 (m, 2H), 6.85 (dd, J = 9.9, 36.0 Hz, 1H),5.19-5.12 (m, 1H), 4.99-4.94 (m, 1H), 4.37-4.08 (m, 2H), 3.13 (s, 3H),1.23 (d, J = 7.2 Hz, 3H) PF3 729 ([M + H]⁺) ¹H NMR (400 MHz, IR (thinfilm) DMSO-d₆) δ 9.26 (br s, 3435, 2926, 1H), 8.14 (s, 1H), 8.09 1667,749 (s, 1H), 8.05 (d, J = cm⁻¹ 8.0 Hz, 1H), 7.85 (s, 1H), 7.61-7.56 (m,2H), 6.84 (dd, J = 10.0, 36.0 Hz, 1H), 5.18-5.13 (m, 1H), 4.22-4.21 (m,2H), 3.17 (s, 3H), 1.04- 1.02 (m, 2H), 0.85- 0.83 (m, 2H) PF4 701 ([M +H]⁺) ¹H NMR (300 MHz, IR (thin film) DMSO-d₆) δ 8.79 (t, J = 3439, 2997,5.4 Hz, 1H), 8.12 (s, 1661, 1031 1H), 8.11-8.05 (m, cm⁻¹ 2H), 7.86 (d, J= 8.4 Hz, 1H), 7.69 (d, J = 8.1 Hz, 1H), 7.62- 7.59 (m, 1H), 6.85 (dd, J= 9.9, 36.0 Hz, 1H), 5.19-5.13(m, 1H), 4.25-4.16 (m, 4H), 3.14 (s, 3H)PF6 597 ([M + H]⁺) ¹H NMR (400 MHz, IR (thin film) DMSO-d₆) δ 8.78 (t, J= 3435, 2997, 6.0 Hz, 1H), 8.12 (s, 1436, 1031 1H), 8.07 (d, J = 8.0cm⁻¹ Hz, 1H), 7.97 (d, J = 6.4 Hz, 1H), 7.71- 7.67 (m, 2H), 7.53- 7.48(m, 1H), 6.83 (dd, J = 10.4, 36.4 Hz, 1H), 5.19-5.14 (m, 1H), 4.23-4.16(m, 2H), 3.14 (s, 2H), 1.26 (d, J = 9.6 Hz, 3H) PF7 595 ([M − H]⁻) ¹HNMR (400 MHz, IR (thin film) DMSO-d₆) δ 8.84 (d, J = 3428, 2925, 7.2 Hz,1H), 8.64 (t, 1650, 1167 J = 6.4 Hz, 1H), 8.10 cm⁻¹ (s, 1H), 8.05 (d, J= 8.0 Hz, 1H), 7.97 (d, J = 6.4 Hz, 1H), 7.68- 7.64 (m, 2H), 7.53- 7.48(m, 1H), 6.83 (dd, J = 10.4, 36.0 Hz, 1H), 5.18-5.13 (m, 1H), 4.52-4.49(m, 1H), 3.99-3.87 (m, 2H), 1.30 (d, J = 7.2 Hz, 3H) PF8 611 ([M + H]⁺)¹H NMR (300 MHz, IR (thin film) DMSO-d₆) δ 8.97 (d, J = 3432, 2927, 7.8Hz, 1H), 8.11 (s, 1647, 1262, 1H), 8.05 (d, J = 7.1 749 cm⁻¹ Hz, 1H),7.97 (d, J = 6.3 Hz, 1H), 7.70- 7.69 (m, 1H), 7.59 (d, J = 8.1 Hz, 1H),7.53- 7.49 (m, 1H), 6.85 (dd, J = 9.9, 35.7 Hz, 1H), 5.19-5.13 (m, 1H),4.99-4.94 (m, 1H), 4.33-4.25 (m, 1H), 4.16-4.13 (m, 1H), 3.22 (s, 3H),1.29 (d, J = 6.9 Hz, 3H) PF10 623 ([M + H]⁺) ¹H NMR (300 MHz, IR (thinfilm) DMSO-d₆) δ 9.24 (br s, 3435, 2999, 1H), 8.12 (s, 1H), 8.04 1656,1030 (d, J = 8.1 Hz, 1H), cm⁻¹ 7.95 (d, J = 6.9 Hz, 1H), 7.69-7.67 (m,1H), 7.56-7.45 (m, 2H), 6.84 (dd, J = 10.2, 36.0 Hz, 1H), 5.17-5.10 (m,1H), 4.18-4.14 (m, 2H), 3.17 (s, 3H), 1.08- 1.06 (m, 2H), 0.84- 0.81 (m,2H) PF12 625 ([M − H]⁻) ¹H NMR (400 MHz, IR (thin film) DMSO-d₆) δ 8.80(t, J = 3433, 3914, 5.6 Hz, 1H), 8.10 (s, 1662 cm⁻¹ 1H), 8.07 (d, J =8.4 Hz, 1H), 7.83 (s, 1H), 7.69-7.67 (m, 1H), 7.64 (s, 1H), 6.81 (dd, J= 10.0, 35.6 Hz, 1H), 5.12-5.07 (m, 1H), 4.23-4.17 (m, 4H), 3.14 (s,3H), 2.42 (s, 3H) PF13 627 ([M + H]⁺) ¹H NMR (300 MHz, IR (thin film)DMSO-d₆) δ 8.84 (d, J = 3414, 2925, 7.8 Hz, 1H) 8.65 (t, 1651 cm⁻¹ J =6.0 Hz, 1H), 8.09 (s, 1H), 8.05 (d, J = 7.8 Hz, 1H), 7.83 (s, 1H), 7.67(d, J = 6.9 Hz, 2H), 6.82 (dd, J = 10.2, 36.0 Hz, 1H), 5.12-5.06 (m,1H), 4.53-4.48 (m, 1H), 4.04-3.86 (m, 2H), 2.42 (s, 3H), 1.32 (d, J =6.9 Hz, 3H) PF14 641 ([M + H]⁺) ¹H NMR (400 MHz, IR (thin film) DMSO-d₆)δ 8.96 (d, J = 3285, 2949, 7.2 Hz, 1H), 8.09 (s, 1656 cm⁻¹ 1H), 8.04 (d,J = 8.8 Hz, 1H), 7.83 (s, 1H), 7.64 (s, 1H), 7.59 (d, J = 8.4 Hz, 1H),6.80 (dd, J = 10.4, 35.6 Hz, 1H), 5.09-5.06 (m, 1H), 4.98-4.94 (m, 1H),4.28-4.26 (m, 1H), 4.15-4.13 (m, 1H), 3.22 (s, 3H), 2.42 (s, 3H), 1.28(d, J = 6.8 Hz, 3H) PF15 639 ([M + H]⁺) ¹H NMR (300 MHz, IR (thin film)DMSO-d₆) δ 9.10 (s, 3462, 2930, 1H), 8.17 (t, J = 6.3 1679, 1116 Hz,1H), 8.10 (s, 2H), cm⁻¹ 8.02 (d, J = 7.5 Hz, 1H), 7.82 (s, 1H), 7.64 (s,1H), 6.83 (dd, J = 9.9, 36.0 Hz, 1H), 5.12- 5.06 (m, 1H), 3.96- 3.87 (m,2H), 2.42 (s, 3H), 1.40-136 (m, 2H), 1.03-0.98 (m, 2H) PF16 653 ([M +H]⁺) ¹H NMR (400 MHz, IR (thin film) DMSO-d₆) δ 9.26 (s, 3445, 1661,1H), 8.12 (s, 1H), 8.05 1031 cm⁻¹ (d, J = 8.0 Hz, 1H), 7.82 (s, 1H),7.64 (s, 1H), 7.58 (d, J = 8.4 Hz, 1H), 6.82 (dd, J = 10.4, 36.0 Hz,1H), 5.11-5.06 (m, 1H), 4.19 (br s, 2H), 3.19 (s, 3H), 2.41 (s, 3H),1.29-1.26 (m, 2H), 0.87-0.79 (m, 2H) PF18 597 ([M + H]⁺) ¹H NMR (300MHz, IR (thin film) DMSO-d₆) δ 8.81 (t, J = 3429, 1661, 5.4 Hz, 1H),8.12 (s, 1030 cm⁻¹ 1H), 8.07 (d, J = 7.8 Hz, 1H), 7.82 (d, J = 10.5 Hz,1H), 7.71- 7.66 (m, 2H), 7.56 (d, J = 9.0 Hz, 1H), 6.83 (dd, J = 10.2,35.7 Hz, 1H), 5.21-5.14 (m, 1H), 4.40-4.37 (m, 1H), 4.25-4.15 (m, 3H),3.14 (s, 3H) PF19 597 ([M + H]⁺) ¹H NMR (400 MHz, IR (thin film)DMSO-d₆) δ 8.84 (d, J = 3431, 2925, 7.2 Hz, 1H), 8.64 (t, 1650 cm⁻¹ J =6.0 Hz, 1H), 8.10 (s, 1H), 8.05 (d, J = 8.4 Hz, 1H), 7.81 (d, J = 10.4Hz, 1H), 7.71- 7.67 (m, 2H), 7.56 (d, J = 8.4 Hz, 1H), 6.81 (dd, J =10.0, 35.6 Hz, 1H), 5.20-5.15 (m, 1H), 4.53-4.95 (m, 1H), 3.99-3.86 (m,2H), 1.30 (d, J = 7.2 Hz, 3H) PF20 609 ([M − H]⁻) ¹H NMR (400 MHz, IR(thin film) DMSO-d₆) δ 8.97 (d, J = 3431, 2925, 7.8 Hz, 1H), 8.11 (s,1650 cm⁻¹ 1H), 8.04 (d, J = 8.7 Hz, 1H), 7.81 (d, J = 10.5 Hz, 1H), 7.71(t, J = 8.4 Hz, 1H), 7.59- 7.53 (m, 2H), 6.82 (dd, J = 10.2, 36.0 Hz,1H), 5.20-5.14 (m, 1H), 4.99-4.94 (m, 1H), 4.28-4.01 (m, 2H), 3.29 (s,3H), 1.28 (d, J = 6.2 Hz, 3H) PF22 623 ([M + H]⁺) ¹H NMR (300 MHz, IR(thin film) DMSO-d₆) δ 9.26 (s, 3429, 1668, 1H), 8.14 (s, 1H), 8.06 1030cm⁻¹ (d, J = 8.4 Hz, 1H), 7.81 (d, J = 9.6 Hz, 1H), 7.71 (t, J = 7.8 Hz,1H), 7.58-7.52 (m, 2H), 6.83 (dd, J = 9.9, 36.0 Hz, 1H), 5.20- 5.14 (m,1H), 4.21 (br s, 2H), 3.18 (s, 3H), 1.28-1.23 (m, 2H), 0.95-0.79 (m, 2H)PF24 657 ([M − H]⁻) ¹H NMR (300 MHz, IR (thin film) DMSO-d₆) δ 8.81-3400, 3316, 8.77 (m, 1H), 8.12 (s, 2928, 1661, 1H), 8.08 (d, J = 8.41267 cm⁻¹ Hz, 1H), 7.99 (s, 1H), 7.87-7.85 (d, J = 8.1 Hz, 1H), 7.70 (d,J = 8.1 Hz, 1H), 7.60 (d, J = 8.4 Hz, 1H), 6.85 (dd, J = 9.9, 35.7 Hz,1H), 5.20-5.14 (m, 1H), 4.25-4.16 (m, 4H), 3.14 (s, 3H) PF25 55-57 658([M + H]⁺) ¹H NMR (300 MHz, DMSO-d₆) δ 8.84 (d, J = 7.5 Hz, 1H), 8.65(t, J = 6.6 Hz, 1H), 8.10 (s, 1H), 8.05 (d, J = 8.4 Hz, 1H), 7.98 (s,1H), 7.87 (d, J = 8.4 Hz, 1H), 7.67 (dd, J = 7.8, 8.1 Hz, 2H), 6.85 (dd,J = 9.9, 35.7 Hz, 1H), 5.20-5.14 (m, 1H), 4.53-4.48 (m, 1H), 3.99-3.89(m, 2H), 1.30 (d, J = 6.9 Hz, 3H) PF26 59-61 671 ([M + H]⁺) ¹H NMR (300MHz, DMSO-d₆) δ 8.97 (d, J = 7.8 Hz, 1H), 8.11 (s, 1H), 8.04 (d, J = 8.1Hz, 1H), 7.98 (s, 1H), 7.87 (d, J = 8.4 Hz, 1H), 7.59 (d, J = 8.1 Hz,2H), 6.85 (dd, J = 9.6, 35.7 Hz, 1H), 5.20- 5.13 (m, 1H), 4.99- 4.94 (m,1H), 4.34- 4.08 (m, 2H), 3.22 (s, 3H), 1.29 (d, J = 7.2 Hz, 3H) PF2763-65 669 ([M + H]⁺) ¹H NMR (300 MHz, DMSO-d₆) δ 9.01 (s, 1H), 8.18-7.97(m, 5H), 7.88 (d, J = 8.4 Hz, 1H), 7.59 (dd, J = 1.8, 8.4 Hz, 1H), 6.86(dd, J = 10.2, 36.3 Hz, 1H), 5.20-5.14 (m, 1H), 3.98-3.87 (m, 2H),1.03-0.99 (m, 2H), 0.87-0.84 (m, 2H) PF28 71-73 683 ([M + H]⁺) ¹H NMR(300 MHz, DMSO-d₆) δ 9.26 (s, 1H), 8.14 (s, 1H), 8.06 (d, J = 8.1 Hz,1H), 7.98 (s, 1H), 7.87 (d, J = 8.4 Hz, 1H), 7.58 (d, J = 8.1 Hz, 1H),7.90 (s, 1H), 6.86 (dd, J = 10.2, 36.0 Hz, 1H), 5.20-5.14 (m, 1H), 4.21(br s, 2H), 3.18 (br s, 3H), 1.30-1.26 (m, 2H), 1.05-1.01 (m, 2H) PF31671 ([M + H]⁺) ¹H NMR (300 MHz, IR (thin film) DMSO-d₆) δ 8.97 (d, J =3430, 1658, 7.2 Hz, 1H), 8.11 (br 1025, 705 s, 1H), 8.05 (d, J = 8.4cm⁻¹ Hz, 1H), 7.93 (br s, 1H), 7.84-7.79 (m, 2H), 7.60 (d, J = 8.1 Hz,1H), 6.86 (dd, J = 10.2, 35.7 Hz, 1H), 5.23-5.17 (m, 1H), 4.99-4.94 (m,1H), 4.33-4.25 (m, 1H), 4.16-4.11 (m, 1H), 3.22 (s, 3H), 1.29 (d, J =7.2 Hz, 3H) PF32 667 ([M − H]⁻) ¹H NMR (300 MHz, IR (thin film) DMSO-d₆)δ 9.10 (br s, 3421, 2925, 1H), 8.17-8.07 (m, 1667, 1166, 3H), 8.02 (d, J= 8.1 750 cm⁻¹ Hz, 1H), 7.93 (s, 1H), 7.84 (s, 1H), 7.80- 7.79 (m, 1H),6.87 (dd, J = 9.9, 36.0 Hz, 1H), 5.23-5.17 (m, 1H), 3.96-3.87 (m, 2H),1.40-1.25 (m, 2H), 1.03-0.99 (m, 2H) PF33 683 ([M + H]⁺) ¹H NMR (300MHz, IR (thin film) DMSO-d₆) δ 9.26 (br s, 3428, 1660, 1H), 8.14 (br s,1H), 1030, 704 8.06 (d, J = 7.8 Hz, cm⁻¹ 1H), 7.92 (br s, 1H), 7.84 (brs, 1H), 7.80 (d, J = 1.5 Hz, 1H), 7.58 (d, J = 8.1 Hz, 1H), 6.87 (dd, J= 9.9, 35.4 Hz, 1H), 5.23- 5.16 (m, 1H), 4.21- 4.19 (m, 2H), 3.29 (s,3H), 1.30-1.26 (m, 2H), 1.04-1.02 (m, 2H) PF35 657 ([M + H]⁺) ¹H NMR(300 MHz, IR (thin film) DMSO-d₆) δ 8.79 (t, J = 3399, 2925, 5.7 Hz,1H), 8.12 (br 1661, 749 s, 2H), 8.08 (d, J = 8.1 cm⁻¹ Hz, 1H), 7.71-7.67(m, 3H), 6.86 (dd, J = 9.9, 36.0 Hz, 1H), 5.21- 5.14 (m, 1H), 4.23- 4.16(m, 4H), 3.14 (s, 3H) PF37 671 ([M + H]⁺) ¹H NMR (300 MHz, IR (thinfilm) DMSO-d₆) δ 8.97 (d, J = 3436, 1660, 7.5 Hz, 1H), 8.11 (s, 1031,702 2H), 8.04 (d, J = 7.8 cm⁻¹ Hz, 1H), 7.71 (s, 2H), 7.59 (d, J = 8.1Hz, 1H), 6.85 (dd, J = 9.9, 36.0 Hz, 1H), 5.20- 5.14 (m, 1H), 4.99- 4.94(m, 1H), 4.33- 4.08 (m, 2H), 3.21 (s, 3H), 1.28 (d, J = 6.9 Hz, 3H) PF39683 ([M + H]⁺) ¹H NMR (400 MHz, IR (thin film) DMSO-d₆) δ 9.26 (br s,3431, 1659, 1H), 8.14-8.11 (m, 1029, 703 2H), 8.05 (d, J = 8.0 cm⁻¹ Hz,1H), 7.73-7.68 (m, 2H), 7.58 (d, J = 8.4 Hz, 1H), 6.84 (dd, J = 10.0,36.0 Hz, 1H), 5.22-5.19 (m, 1H), 4.23-4.19 (m, 2H), 3.19 (s, 3H), 1.29-1.28 (m, 2H), 1.08- 1.03 (m, 2H) PF41 645 ([M − H]⁻) ¹H NMR (400 MHz, IR(thin film) DMSO-d₆) δ 8.80 (t, J = 3411, 2927, 5.6 Hz, 1H), 8.17 (s,1670, 1261, 1H), 8.12-8.07 (m, 750 cm⁻¹ 3H), 7.94 (s, 1H), 7.72 (d, J =8.4 Hz, 1H), 6.94 (dd, J = 10.0, 35.6 Hz, 1H), 5.39- 5.32 (m, 1H), 4.23-4.27 (m, 4H), 3.14 (s, 3H) PF42 105-107 645 ([M − H]⁻) ¹H NMR (300 MHz,CDCl₃) δ 7.88 (s, 1H), 7.80 (d, J = 8.6 Hz, 1H), 7.64 (s, 1H), 7.63-7.51 (m, 3H), 6.81 (t, J = 6.5 Hz, 1H), 6.44 (d, J = 7.5 Hz, 1H), 5.88(dd, J = 32.5, 9.6 Hz, 1H), 4.84- 4.61 (m, 2H), 3.93 (qd, J = 9.0, 6.5Hz, 2H), 1.51 (d, J = 7.0 Hz, 3H) PF43 661 ([M + H]⁺) ¹H NMR (400 MHz,IR (thin film) DMSO-d₆) δ 8.97 (d, J = 3409, 3299, 7.2 Hz, 1H), 8.17 (s,2988, 1651, 1H), 8.12 (d, J = 8.4 750 cm⁻¹ Hz, 1H), 8.06 (d, J = 5.7 Hz,1H), 7.94 (s, 2H), 7.60 (d, J = 5.7 Hz, 1H), 6.92 (dd, J = 10.0, 35.6Hz, 1H), 5.39-5.34 (m, 1H), 4.99-4.93 (m, 1H), 4.35-4.24 (m, 1H),4.15-4.09 (m, 1H), 3.22 (s, 3H), 1.29 (d, J = 6.8 Hz, 3H) PF44 52-54 659([M + H]⁺) ¹H NMR (300 MHz, CDCl₃) δ 9.12 (s, 2H), 8.17-7.95 (m, 6H),6.95 (dd, J = 9.9, 36.0 Hz, 1H), 5.40-5.34 (m, 1H), 3.96-3.90 (m, 2H),1.41-1.37 (m, 2H), 1.03-0.99 (m, 2H) PF45 62-65 673 ([M + H]⁺) ¹H NMR(300 MHz, DMSO-d₆) δ 9.26 (s, 1H), 8.16 (d, J = 5.7 Hz, 2H), 8.09 (s,1H), 8.07 (d, J = 6.3 Hz, 1H), 7.95 (s, 1H), 7.65 (d, J = 5.7 Hz, 1H),6.93 (dd, J = 7.8, 26.7 Hz, 1H), 5.38-5.34 (m, 1H), 4.40-4.20 (m, 2H),3.18 (s, 3H), 1.28-1.27 (m, 2H), 1.04-1.02 (m, 2H) PF47 133-136 593([M + H]⁺) ¹H NMR (300 MHz, DMSO-d₆) δ 8.79 (t, J = 5.4 Hz, 1H), 8.12(s, 1H), 8.07 (d, J = 7.8 Hz, 1H), 7.71-7.60 (m, 2H), 7.49 (s, 2H), 6.70(dd, J = 35.7, 10.2 Hz, 1H), 5.04- 4.96 (m, 1H), 4.25- 4.17 (m, 4H),3.15 (s, 3H), 2.38 (s, 3H) PF48 90-93 593 ([M + H]⁺) ¹H NMR (400 MHz,CDCl₃) δ 8.83 (d, J = 8.0 Hz, 1H), 8.63 (d, J = 6.4 Hz, 1H), 8.08 (s,1H), 8.05 (d, J = 7.6 Hz, 1H), 7.66 (d, J = 8.0 Hz, 1H), 7.62 (s, 1H),7.47 (s, 2H), 6.78 (dd, J = 9.6, 35.6 Hz, 1H), 5.02-4.95 (m, 1H),4.54-4.47 (m, 1H), 4.03-3.85 (m, 2H), 2.35 (s, 3H), 1.30 (d, J = 8.0 Hz,3H) PF49 71-74 607 ([M + H]⁺) ¹H NMR (300 MHz, DMSO-d₆) δ 8.96 (d, J =7.2 Hz, 1H), 8.09 (s, 1H), 8.04 (d, J = 8.1 Hz, 1H), 7.62 (s, 1H), 7.59(d, J = 8.1 Hz, 1H), 7.47 (s, 2H), 6.94 (dd, J = 10.2, 35.1 Hz, 1H),5.00-4.94 (m, 2H), 4.48-4.00 (m, 2H), 3.22 (s, 3H), 2.37 (s, 3H), 1.28(d, J = 6.9 Hz, 3H) PF50 75-78 605 ([M + H]⁺) ¹H NMR (400 MHz, DMSO-d₆)δ 9.09 (s, 1H) 8.16 (t, J = 8.4 Hz, 1H), 8.09-8.06 (m, 2H), 8.01 (d, J =7.6 Hz, 1H), 7.61 (s, 1H), 7.48 (s, 2H), 6.79 (dd, J = 10.0, 36.0 Hz,1H), 5.03-4.98 (m, 1H), 3.97-3.88 (m, 2H), 2.35 (s, 3H), 1.40- 1.37 (m,2H), 1.03- 1.00 (m, 2H) PF51 86-89 619 ([M + H]⁺) ¹H NMR (300 MHz,DMSO-d₆) δ 9.26 (br s, 1H), 8.12 (s, 1H), 8.06 (d, J = 8.1 Hz, 1H), 7.61(s, 1H), 7.57 (d, J = 8.1 Hz, 1H), 7.47 (s, 2H), 6.82 (dd, J = 9.9, 36.0Hz, 1H), 5.00- 4.97 (m, 1H), 4.21 (br s, 2H), 3.18 (br s, 3H), 2.35 (s,3H) 1.30- 1.26 (m, 2H), 1.05- 1.02 (m, 2H) PF60 609 ([M + H]⁺) ¹H NMR(300 MHz, IR (thin film) DMSO-d₆) δ 8.75 (d, J = 3431, 2925, 7.5 Hz,1H), 8.59 (t, 1650 cm⁻¹ J = 6.0 Hz, 1H), 7.88 (s, 3H), 7.71 (d, J = 8.1Hz, 1H), 7.54 (d, J = 7.8 Hz, 1H), 6.66 (dd, J = 10.2, 36.6 Hz, 1H),4.73-4.60 (m, 1H), 4.52-4.45 (m, 1H), 4.05-3.85 (m, 2H), 1.62 (t, J =18.9 Hz, 3H), 1.31 (d, J = 6.9 Hz, 3H) PF62 623 ([M + H]⁺) ¹H NMR (300MHz, IR (thin film) DMSO-d₆) δ 9.02 (s, 3431, 2925, 1H), 8.16 (t, J =6.3 1650 cm⁻¹ Hz, 1H), 7.88 (s, 2H), 7.78-7.70 (m, 3H), 6.67 (dd, J =10.5, 36.6 Hz, 1H), 4.68- 4.65 (m, 1H), 3.96- 3.91 (m, 2H), 1.68 (t, J =18.9 Hz, 3H), 1.41- 1.35 (m, 2H), 1.23- 1.20 (m, 2H) PF82 648 ([M − H]⁻)¹H NMR (400 MHz, ¹⁹F NMR CDCl₃) δ 8.16 (s, 1H), (376 MHz, 7.82 (s, 1H),7.75 (d, J = CDCl₃) δ 8.3 Hz, 1H), 7.60 (d, −58.34, −69.35, J = 8.2 Hz,1H), 7.43 −72.47, −111.91 (s, 2H), 6.29-6.21 (m, 1H), 5.81 (dd, J =32.6, 9.6 Hz, 1H), 4.60 (p, J = 8.9 Hz, 1H), 4.52 (d, J = 4.7 Hz, 2H),4.00 (qd, J = 8.9, 6.5 Hz, 2H) PF88 663 ([M − H]⁻) ¹H NMR (500 MHz, ¹⁹FNMR CDCl₃) δ 8.55 (t, J = (471 MHz, 5.1 Hz, 1H), 8.19 (t, J = CDCl₃) δ6.1 Hz, 1H), 7.83 (d, −58.18, −69.35 J = 1.7 Hz, 1H), 7.75 (d, J = 8.8Hz), −70.58 (dd, J = 8.2, 1.8 Hz, (t, J = 9.0 Hz), −111.95 1H),7.66-7.56 (m, (d, J = 32.7 Hz) 1H), 7.43 (s, 2H), 5.82 (dd, J = 32.6,9.6 Hz, 1H), 4.80 (d, J = 5.1 Hz, 2H), 4.61 (p, J = 8.8 Hz, 1H), 4.46(qd, J = 8.9, 5.9 Hz, 2H) PF94 649 ([M − H]⁻) ¹H NMR (400 MHz, ¹⁹F NMRCDCl₃) δ 9.03 (s, 1H), (376 MHz, 7.90 (d, J = 1.7 Hz, CDCl₃) δ 1H), 7.83(dd, J = 8.1, −59.21, −69.30, 1.7 Hz, 1H), 7.65 (d, J = −70.67, −112.028.1 Hz, 1H), 7.44 (s, 2H), 7.11 (s, 1H), 5.86 (dd, J = 32.5, 9.5 Hz,1H), 4.68-4.57 (m, 1H), 4.56 (d, J = 5.4 Hz, 2H), 4.43 (qd, J = 9.0, 5.9Hz, 2H) PF96 663 ([M − H]⁻) ¹H NMR (400 MHz, ¹⁹F NMR CDCl₃) δ 9.68 (t, J= (376 MHz, 6.0 Hz, 1H), 7.93- CDCl₃) δ 7.87 (m, 1H), 7.82 −59.24 (d, J= (dd, J = 8.1, 1.7 Hz, 1.7 Hz), −69.32 (d, 1H), 7.64 (d, J = 8.1 J =2.2 Hz), −70.63, Hz, 1H), 7.45 (s, 2H), −109.75-−114.23 (m) 7.36 (d, J =8.1 Hz, 1H), 6.08-5.76 (m, 1H), 5.57-5.34 (m, 1H), 4.62 (p, J = 8.9 Hz,1H), 4.52-4.22 (m, 2H), 1.59 (d, J = 6.7 Hz, 3H) PF98 675 ([M − H]⁻) ¹HNMR (400 MHz, ¹⁹F NMR CDCl₃) δ 9.01 (s, 1H), (376 MHz, 7.93-7.84 (m,1H), CDCl₃) 7.80 (dd, J = 8.1, 1.7 δ −58.84 (t, J = 1.8 Hz, 1H), 7.53(d, J = Hz), −69.30 (d, J = 2.3 8.3 Hz, 1H), 7.43 (s, Hz), −70.82 (d, J= 18 2H), 6.61 (s, 1H), 5.85 Hz) −112.05 (dd, J = 32.5, 9.6 Hz, 1H),4.61 (p, J = 8.8 Hz, 1H), 4.47 (qd, J = 9.1, 5.9 Hz, 2H), 1.96- 1.86 (m,2H), 1.38- 1.26 (m, 2H)

BAW, CEW, & CL Rating Table % Control (or Mortality) Rating 50-100 AMore than 0-Less than 50 B Not Tested C No activity noticed in thisbioassay D

GPA & YFM Rating Table % Control (or Mortality) Rating 80-100 A Morethan 0-Less than 80 B Not Tested C No activity noticed in this bioassayD

TABLE ABC Biological Results Pests No. BAW CL GPA YFM F1 A A C C F2 A AC C F3 A A A C F4 A A C C F5 A A C C F6 A A C C F7 A A C C F8 A A C C F9A A C C F10 A A C C F11 A A C C F12 A A C C F13 A A C C F14 A A C C F15A A C C F16 A A C C F17 A A C C F18 A A C C F19 A A C C F20 A A C C F21A A C C F22 A A C C F23 A A C C F24 A A C C F25 A A C C F26 A A C C F27A A C C F28 A A C C F29 A A C C F30 A A C C F31 A A C C F32 A A C C F33A A C A F34 A A C A F35 A A C A F36 A A C A F37 A A C A F38 A A C A F39A A C A F40 A A C A F41 A A C A F42 A A C A F43 A A C A F44 A A C A F45A A C A F46 A A C A F47 A A C C F48 A A C C F49 A A C C F50 A A C C F51A A C C F52 A A C A F53 A A C A F54 A A C C F55 A A C C F56 A A C C F57A A C C F58 A A C C F59 A A C A F60 A A C A F61 A A C A F62 A A C C F63A A C C F64 A A C C F65 A A C C F66 A A C C F67 A A C C F68 A A C A F69A A C A F70 A A C A F71 A A C B F72 A A C A F73 A A C A F74 A A C A F75A A C A F76 A A C A F77 A A C A F78 A A C A F79 A A C A F80 A A C A F81A A C A F82 A A C A F83 A A C A F84 A A C A F85 A A C A F86 A A C A F87A A C C F88 A A C C F89 A A C C F90 A A C C F91 A A C C F92 A A C C F93A A C C F94 A A C C F95 A A C C F96 A A C C F97 A A C C F98 A A C C F99A A C A F100 A A C C F101 A A C C F102 A A C A F103 A A C B F104 A A C CF105 A A C C F106 A A C C F107 A A C C F108 A A C C F109 A A C C F110 AA C C F111 A A C C F112 A A C C F113 A A C A F114 A A C A F115 A A C BF116 A A C A F117 A A C C F118 A A C B F119 A A C B F120 A A C B F121 AA C C F122 A A C B F123 A A C C F124 A A C C F125 A A C C F126 A A C CF127 A A C C F128 A A C C F129 A A C C F130 A A C A F131 A A C A F132 AA C B F133 A A C B F134 A A C B F135 A A C B F136 A A C B F137 A A C BF138 A A C A F139 A A C A F140 A A C C F141 A A C A F142 A A C A F143 AA C A F144 A A C A F145 A A C C F146 A A B B F147 A A C A F148 A A C DF150 A A C C F153 A A C A F154 A A C C F155 A A A A F157 A A C A F158 AA C D F159 A A C A F160 A A A A F161 A A C A F162 A A C D F163 A A C AF164 A A C B F165 A A C B F166 A A C C F167 A A A A F168 A A C C F169 AA C C F170 A A C C F171 A A C C F172 A A C B F173 A A C D F174 A A C CF175 A A C C F176 A A C C F177 A A A A F178 A A C C F180 A A A D F181 AA C C F182 A A C C F183 A A C C F184 A A C C F185 A A C C F186 A A C CF187 A A C C F188 A A C C F189 A A C C F190 A A C C F191 A A C C F192 AA C C F193 A A C C F194 A A C C F195 A A C C F196 A A C C F197 A A C CF198 A A C C F199 A A C C F200 A A C C F201 A A C C F202 A A C C F203 AA C C F204 A A C C F205 A A C B F206 A A C D F207 A A C C F208 A A C AF209 A A C A F210 A A C B F211 A A C D F212 A A C C F213 A A C C F214 AA C C F215 A A C C F216 A A C C F217 A A C C PF1 A A C A PF2 A A C A PF3A A C A PF4 A A C A PF6 A A A A PF7 A A C B PF8 A A C B PF10 A A C APF12 A A C B PF13 A A C B PF14 A A C A PF15 A A C B PF16 A A B A PF18 AA C B PF19 A A C B PF20 A A C B PF22 A A C B PF24 A A A A PF25 A A C BPF26 A A C C PF27 A A A B PF28 A A C C PF31 A A C B PF32 A A B A PF33 AA C B PF35 A A C B PF37 A A C B PF39 A A C B PF41 A A C C PF42 A A C CPF43 A A C C PF44 A A C C PF45 A A C C PF47 A A C D PF48 A A C C PF49 AA C C PF50 A A C C PF51 A A C C PF60 A A C C PF62 A A C D PF82 A A C APF88 A A C C PF94 A A C A PF96 A A C C PF98 A A C C

Comparative Data

Bioassays on BAW and CL were conducted according to the proceduresoutlined in Example A: Bioassays on Beet Armyworm (“BAW”) and CabbageLooper (“CL”) using the indicated concentrations. The results areindicated in Table CD1 and Table CD2.

TABLE CD1

5 μg/cm² 0.5 μg/cm² 0.05 μg/cm² No. R¹⁰ BAW CL BAW CL BAW CL FC1 H 100*100 100 100  0  0 F22 Cl 100  100 100 100 100 100 F19 Br 100  100 100100 100 100 F6  CH₃ 100 100 100 100 F1  CF₃ 100  100 100 100 100 100*Percent control (or mortality)

TABLE CD2

5 μg/cm² 0.5 μg/cm² 0.05 μg/cm² No. R¹⁰ BAW CL BAW CL BAW CL FC2 H 100*100 100 100  0  0 F23 Cl 100  100 100 100  81 100 F18 Br 100  100 100100 100 100 F67 I 100  100 100 100 100 100 F7  CH₃ 100 100 100 100 F2 CF₃ 100  100 100 100 100 100 *Percent control (or mortality)

1. A molecule having the following formula

wherein: (A) R¹, R⁵, R⁶, R¹¹, and R¹² are each independently selectedfrom the group consisting of H, F, Cl, Br, I, CN, (C₁-C₆)alkyl,(C₁-C₆)haloalkyl, (C₁-C₆)alkoxy, and (C₁-C₄)haloalkoxy; (B) R², R³, andR⁴ are each independently selected from the group consisting of H, F,Cl, Br, I, CN, (C₁-C₆)alkyl, (C₂-C₆)alkenyl, (C₂-C₆)alkynyl,(C₁-C₆)haloalkyl, (C₁-C₆)alkoxy, and (C₁-C₆)haloalkoxy; (C) R⁷ is(C₁-C₆)haloalkyl; (D) R⁹ is selected from the group consisting of (F),H, F, Cl, Br, I, CN, (C₁-C₄)alkyl, (C₁-C₄)haloalkyl, (C₁-C₄)alkoxy, and(C₁-C₄)haloalkoxy; (E) R¹⁰ is selected from the group consisting of (F),F, Cl, Br, I, CN, (C₁-C₆)alkyl, (C₂-C₆)alkenyl, (C₂-C₆)alkynyl,(C₁-C₆)haloalkyl, (C₁-C₆)alkoxy, and (C₁-C₆)haloalkoxy; (F) R⁹ and R¹⁰together can optionally form a 3- to 5-membered saturated orunsaturated, hydrocarbyl link, wherein said hydrocarbyl link mayoptionally be substituted with one or more substituents independentlyselected from the group consisting of F, Cl, Br, I, CN, OH, and oxo; (G)Q¹ and Q² are each independently O or S; (H) R¹³ is selected from thegroup consisting of H, (C₁-C₆)alkyl, (C₂-C₆)alkenyl, (C₁-C₆)haloalkyl,(C₁-C₆)alkoxy, and (C₁-C₆)haloalkoxy; (I) R¹⁴ is selected from the groupconsisting of (K), (O), H, (C₁-C₄)alkyl, (C₂-C₆)alkenyl,(C₁-C₆)haloalkyl, (C₁-C₆)alkoxy, and (C₁-C₆)haloalkoxy; (J) R¹⁵ isselected from the group consisting of (K), H, (C₁-C₆)alkyl,(C₂-C₆)alkenyl, (C₁-C₆)haloalkyl, (C₁-C₆)alkoxy, and (C₁-C₆)haloalkoxy;(K) R¹⁴ and R¹⁵ together can optionally form a 2- to 5-memberedsaturated, hydrocarbyl link, wherein said hydrocarbyl link mayoptionally be substituted with one or more substituents independentlyselected from the group consisting of F, Cl, Br, I, and CN; (L) L isselected from the group consisting of (1) a bond connecting C(R¹⁴)(R¹⁵)to C(=Q²), and (2) a (C1-C₆)alkyl wherein said alkyl is optionallysubstituted with one or more substituents independently selected fromthe group consisting of F, Cl, CN, OH, and oxo; (M) X is selected fromthe group consisting of (1) a bond connecting C(=Q²) to R¹⁷, and (2) aN, O, and S connecting C(=Q²) to R¹⁷; (N) R¹⁶ is selected from the groupconsisting of (O), H, (C₁-C₆)alkyl, (C₂-C₆)alkenyl, (C₁-C₆)haloalkyl,(C₁-C₆)alkoxy, (C₂-C₆)alkenyloxy, (C₁-C₆)haloalkoxy, amino, andNHC(O)O(C₁-C₆)alkyl; (O) R¹⁴ and R¹⁵ together can optionally form a 2-to 4-membered saturated, hydrocarbyl link, which may contain one or moreheteroatoms selected from the group consisting of nitrogen, sulfur, andoxygen, wherein said hydrocarbyl link may optionally be substituted withone or more substituents independently selected from the groupconsisting of F, Cl, Br, I, CN, OH, and oxo; (P) R¹⁷ is selected fromthe group consisting of H, (C₁-C₆)alkyl, (C₂-C₆)alkenyl, (C₂-C₆)alkynyl,(C₁-C₆)haloalkyl, (C₂-C₆)haloalkenyl, (C₃-C₆)halocycloalkyl,(C₁-C₆)alkoxy, (C₃-C₆)cycloalkyl, (C₂-C₆)alkenyloxy, (C₁-C₆)haloalkoxy,and (C₁-C₆)alkyl(C₃-C₆)cycloalkyl; (Q) R¹⁶ and R¹⁷ together canoptionally form a 2- to 6-membered saturated, hydrocarbyl link, whichmay contain one or more heteroatoms selected from the group consistingof nitrogen, sulfur, and oxygen, wherein said hydrocarbyl link mayoptionally be substituted with one or more substituents independentlyselected from the group consisting of F, Cl, Br, I, CN, OH, and oxo; andagriculturally acceptable acid addition salts, salt derivatives,solvates, ester derivatives, crystal polymorphs, isotopes, resolvedstereoisomers, and tautomers, of the molecules of Formula One.
 2. Amolecule according to claim 1 wherein R¹, R³, R⁴, R⁵, R⁶, R⁹, R¹¹, R¹²,R¹³, R¹⁴ R¹⁵, R¹⁶, and R¹⁷ are H.
 3. A molecule according to claim 1wherein R² is F, Cl, Br, or CH₃.
 4. A molecule according to claim 1wherein R³ is F, Cl, Br, or CH═CH₂.
 5. A molecule according to claim 1wherein R⁴ is Cl, Br, or CH₃.
 6. A molecule according to claim 1 whereinR², R³, and R⁴ are CI.
 7. A molecule according to claim 1 wherein R⁷ is(C₁-C₆)haloalkyl.
 8. A molecule according to claim 1 wherein R⁷ is CF₃,CF₂CH₃, or CF₂CH₂CH₃.
 9. A molecule according to claim 1 wherein R¹⁰ isCl, Br, I, CH₃, or CF₃.
 10. A molecule according to claim 1 wherein Q¹and Q² are O.
 11. A molecule according to claim 1 wherein R¹³, R¹⁴, andR¹⁵ are CH₃ or CH₂CH₃.
 12. A molecule according to claim 1 wherein R¹⁴and R¹⁵ together form a 2-membered saturated, hydrocarbyl link.
 13. Amolecule according to claim 1 wherein L is a bond connecting C(R¹⁴)(R¹⁵)to C(=Q²).
 14. A molecule according to claim 1 wherein X is a bondconnecting C(=Q²) to R¹⁷.
 15. A molecule according to claim 1 wherein Xis N connecting C(=Q²) to R¹⁷.
 16. A molecule according to claim 1wherein R¹⁶ is CH₃, CH₂CH₃, OCH₃, OCH₂CH═CH₂, NH₂, or NHC(O)OC(CH₃)₃.17. A molecule according to claim 1 wherein R¹⁴ and R¹⁶ together form a2- to 4-membered saturated, hydrocarbyl link, which may contain one ormore oxygen heteroatoms.
 18. A molecule according to claim 1 wherein R¹⁷is CH₂CH₃, CH₂CH₂CH₂CH₃, CH₂CH₂CH(CH₃)₂, CH₂CH═CH₂, CH₂C≡CH, CH₂CHF₂,CH₂CF₃, CH₂CH₂CF₃, CH₂CF₂CH₃, CH(CH₃)CF₃, CH₂CH₂CH₂CF₃, CH═CHCH₂CF₃,3,3-difluorocyclobutyl, CH₂CH₂cyclopropyl, and CH₂cyclobutyl.
 19. Amolecule according to claim 1 wherein (A) R¹, R⁵, R⁶, R¹, and R¹² are H;(B) R², R³, and R⁴ are each independently selected from the groupconsisting of H, F, Cl, Br, (C₁-C₆)alkyl, and (C₂-C₆)alkenyl; (C) R⁷ is(C₁-C₆)haloalkyl; (D) R⁹ is H; (E) R¹⁰ is selected from the groupconsisting of Cl, Br, I, (C₁-C₆)alkyl, and (C₁-C₆)haloalkyl; (G) Q¹ andQ² are O; (H) R¹³ is selected from the group consisting of H and(C₁-C₆)alkyl; (I) R¹⁴ is selected from the group consisting of (K), (O),H, and (C₁-C₄)alkyl; (J) R¹⁵ is selected from the group consisting of(K), H, and (C₁-C₆)alkyl; (K) R¹⁴ and R¹⁵ together can optionally form a2- to 5-membered saturated, hydrocarbyl link; (L) L is a bond connectingC(R¹⁴)(R¹⁵) to C=Q²; (M) X is selected from the group consisting of (1)a bond connecting C(=Q²) to R¹⁷, and (2) a N, O, and S connecting C(=Q²)to R¹⁷; (N) R¹⁶ is selected from the group consisting of (O), H,(C₁-C₆)alkyl, (C₁-C₆)alkoxy, (C₂-C₆)alkenyloxy, amino, andNHC(O)O(C₁-C₆)alkyl; (O) R¹⁴ and R¹⁶ together can optionally form a 2-to 4-membered saturated, hydrocarbyl link, which may contain one or moreoxygen heteroatoms; (P) R¹⁷ is selected from the group consisting of H,(C₁-C₆)alkyl, (C₂-C₆)alkenyl, (C₂-C₆)alkynyl, (C₁-C₆)haloalkyl,(C₁-C₆)haloalkenyl, (C₃-C₆)halocycloalkyl, and(C₁-C₆)alkyl(C₃-C₆)cycloalkyl.
 20. A molecule according to claim 1wherein said molecule is selected from one of the molecules in Table 2.21. A molecule according to claim 1 wherein said molecule is selectedfrom one of the molecules in Table
 1. 22. A pesticidal compositioncomprising a molecule according to claim 1 further comprising one ormore active ingredients.
 23. A pesticidal composition according to claim22 wherein said active ingredient is from AIGA.
 24. A pesticidalcomposition according to claim 22 wherein said active ingredient isselected from the group consisting of AI-1, 1,3-dichloropropene,chlorpyrifos, chlorpyrifos-methyl, hexaflumuron, methoxyfenozide,noviflumuron, spinetoram, spinosad, sulfoxaflor, and sulfuryl fluoride.25. A pesticidal composition comprising a molecule according to claim 1further comprising one or more MoA Materials.
 26. A pesticidalcomposition according to claim 25 wherein said MoA Material is fromMoAMGA.
 27. A pesticidal composition comprising a molecule according toclaim 1 and a seed.
 28. A process to control a pest said processcomprising applying to a locus, a pesticidally effective amount of apesticidal composition wherein said pesticidal composition comprises amolecule according to claim 1.